ASCO's Policy Research Articles

Phase II randomized, open-label study of cetuximab (Cet) and bevacizumab (Bev) in combination with paclitaxel (P) and carboplatin (C) in patients with stageIII/IV non-small cell lung cancer (NSCLC)

8046^ Background: Cet, a monoclonal antibody (mAb) that specifically targets epidermal growth factor receptor (EGFR) and Bev (anti-VEGF mAb) combined with chemotherapy has resulted in superior survival compared to chemotherapy alone in some stage IV NSCLC trials. Combining both mAb's with chemotherapy might increase survival in stage IV NSCLC pts. Methods: Chemotherapy naïve advanced NSCLC patients with ECOG status <1, adequate hematologic, hepatic, and renal function received Cet (400 mg/m2 on Day 1 as initial dose and weekly thereafter at 250 mg/m2) plus Bev (15 mg/kg on Day 8 of each 3-week cycle) for 6 cycles in combination with either 6 cycles (Arm A) or 3 cycles (Arm B) of P (200 m/kg) and C (AUC=6) on Day 1 of each 3-week cycle. Patients without progressive disease (PD) after 6 cycles continued Cet until PD or other withdrawal criteria were met. Comparison of progression-free survival (PFS) for arm A vs B is the primary objective. Results: Accrual is completed. Data are available for 85 pts: 47% women, median age 65 yrs, and 88% Caucasian. Median PFS for arm A was 6.0 vs 4.2 months for arm B, hazard ratio of 0.57 for arm A relative to arm B. Objective response was Arm A=31% and B=30%. Most frequent AEs ≥Grade 3 in pts were neutropenia [9 (10.6%), A=8, B=1], fatigue [8 (9.4%), A=4, B=4], dermatitis acneiform [6 (7.1%), A=3, B=3].13 pts withdrew due to AEs (A=4, B=9), 4 were related to Cet (2 per arm). Two pts discontinued due to death (A=2, B=0) unrelated to Cet. Conclusions: Adding both mAb's to PC resulted in acceptable toxicity. The trend for superior PFS with 6 courses of PC suggests that 3 courses of PC are not optimal. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

The influence of unscheduled biopsies on prostate cancer detection in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial

1504^ Background: REDUCE is an ongoing 4-year, international, randomized, placebo-controlled study investigating the effect of dutasteride on the incidence of biopsy-detectable prostate cancer (PCa). We assessed the influence of prostate specific antigen (PSA)-driven, unscheduled biopsies on PCa detection. Methods: Eligible subjects were aged 50–75 years with serum PSA 2.5–10 ng/mL (50–60 years) or 3–10 ng/mL (>60 years) and a negative 6–12-core biopsy ≤6 months before enrollment. Protocol-mandated transrectal ultrasound directed biopsies (10 cores) were taken at 2 and 4 years; we report unblinded 2-year data. Results: Of the 8108 subjects in the efficacy population (subjects with no PCa in baseline biopsy as assessed by Central lab and who took at least one dose of study medication), 356 subjects (4.4%) underwent an unscheduled biopsy (0–18 months), and 6460 subjects (79.7%) underwent a protocol-mandated (scheduled) biopsy (19–24 months). Rising PSA was the primary reason for an unscheduled biopsy. PCa was diagnosed in 60 subjects (16.9%) at an unscheduled biopsy compared with 950 subjects (14.7%) at scheduled biopsy. Subjects with PCa on unscheduled, compared with scheduled, biopsy had higher baseline PSA (6.63 vs. 6.06 ng/mL), lower % free PSA (13.2% vs. 15.5%); there was no difference in the mean number of baseline biopsy cores (8.6 vs. 8.4). Conclusions: Although unscheduled biopsies in REDUCE were slightly more likely to result in a cancer diagnosis and have a higher Gleason score, the small number of such biopsies (356/6591, 5.4% of subjects biopsied) would not cause a significant ascertainment bias. This contrasts the prostate cancer prevention trial (PCPT), where close to 40% of subjects had for-cause biopsies (most often PSA-driven), creating a substantial detection bias for high-grade cancers. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Nab-paclitaxel and bevacizumab as first-line therapy in patients with unresectable stage III and IV melanoma

9061^ Background: Nab-paclitaxel (Abraxane) increases intra-tumoral concentrations of paclitaxel and has efficacy superior to that of paclitaxel for the treatment of metastatic breast cancer (J Clin Oncol 2005:23:7794–7803). Nab-paclitaxel demonstrated single agent activity in metastatic melanoma. (ASCO 2005:7558) Bevacizumab is a monoclonal antibody that targets VEGF resulting in inhibition of tumor angiogenesis and enhances tumor response to paclitaxel. (NEJM 2007:357:2666–2676) Methods: Eligible were chemotherapy-naïve patients with unresectable stage III or IV melanoma, ECOG performance status of 0–1, and adequate organ function. The treatment regimen was given in a 28-day cycle in which nab-paclitaxel 150 mg/m2 was administered on days 1, 8, and 15 and bevacizumab 10mg/kg on days 1 and 15 until disease progression or dose limiting toxicity. Response assessments were made by RECIST criteria every 2 cycles. Results: Forty-one patients have been treated since 08/15/07. Over 50% of the patients had stage IV, MIc disease. The median duration of follow-up for progression-free survival from start of protocol treatment is 5.3 months. Progression-free survival at 4 months is 83%,(95%CI:69%-97%). Median progression free survival is 6.25 months (95%CI: 5.63–9.41). The median duration of follow-up for survival is 4.7 months. Three patients have died and 38 patients remain alive. The 6 month survival rate is 91% (95%CI:79%-100%).The 12 month survival rate is 83% (95% CI:65%-100%). The median duration of overall survival has not been reached yet. Dose modifying toxicities consisted primarily of neutropenia, neuropathy, and hypertension. Conclusions: Early experience suggests that nab-paclitaxel and bevacizumab is an effective and well-tolerated regimen as first-line therapy in patients with metastatic melanoma. The study is ongoing with an accrual target of 50 patients. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Randomized, double blind, multicenter, phase II study of pemetrexed (PEM), carboplatin (CARBO), bevacizumab (BEV) with enzastaurin (ENZ) or placebo (PBO) in chemotherapy-naive patients with stage IIIB/IV non-small cell lung cancer (NSCLC): Hoosier Oncology Group (HOG) LUN06–116

8035^ Background: Pre-clinical data suggests that ENZ and BEV may have complementary effects in inhibiting angiogenesis. This study compared ENZ vs PBO in combination with PEM+CARBO+ BEV. Methods: Pts ≥18 years of age, non-squamous NSCLC, no prior systemic therapy, disease measurable by RECIST, and ECOG PS 0–1 were randomized. Pts received either PBO or 500 mg ENZ daily after loading dose of 375 mg orally, TID, on day 1, cycle 1. Starting on day 8, cycle 1, patients received PEM 500mg/m2, CARBO AUC 6 and BEV 15mg/kg, intravenously, every 21 days. After 4 cycles, pts continued on BEV+ENZ or BEV+PBO. Pts were stratified by ECOG status, disease stage and site with a planned sample size of 90 pts. Primary end point was progression-free survival (PFS). Secondary end points included objective response rate (ORR) and toxicity. Results: Study was terminated after a planned interim analysis for safety and efficacy. From October 2007 to July 2008, 40 pts were enrolled: 20 in each arm. Median age was 60.5 years (range: 44 to 78); M 52.5%, F 47.5%; ECOG PS 0/1 52.5% and 47.5%; stage IIIB/IV 15% and 85%. Baseline characteristics were well matched. The PEM+CARBO+BEV+ENZ arm received a median of 3 cycles of therapy and the PEM+CARBO+BEV+PBO arm 4 cycles. Median PFS was 4.3 mo and 4.2 mo for ENZ and PBO, respectively (unadjusted HR: 0.94, 95% CI [0.39, 2.33]). ORR for ENZ and PBO was 20% and 25%, respectively. Overall, grade 3/4 toxicities were similar in both arms. One patient in ENZ arm experienced a grade 3/4 hemorrhage (vs. none in the PBO arm). Two patients experienced a GI perforation (1 on each arm): 1 resulted in death on the PBO arm. Both patients had a history of diverticulosis. Conclusions: Based upon the results of this interim efficacy analysis, addition of ENZ to PEM+CARBO+BEV will not significantly prolong PFS in patients with stage IIIB/IV NSCLC. This combination does not warrant further study in NSCLC. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

A phase I dose escalation study of AUY922, a novel HSP90 inhibitor, in patients with advanced solid malignancies

3532^ Background: AUY922, a novel isoxazole-based HSP90 inhibitor, causes the degradation of multiple cellular tumor promoting targets. Preclinical evidence suggests broad anti-tumor activity of AUY922, warranting clinical development. Methods: Single agent AUY922 was administered as IV infusion over 1h once a week to patients (pts) with advanced solid malignancies, utilizing a Bayesian design for dose-escalation. The primary endpoint was determination of the maximum tolerated dose of AUY922; secondary endpoints included safety, tolerability, preliminary activity, PK and PD. Results: Between Jul 2007 and Dec 2008, 44 pts with were treated at dose levels of 2 mg/m2 (3pts), 4 mg/m2 (4pts), 8 mg/m2 (5pts), 16 mg/m2 (7pts), 22 mg/m2 (11pts), 28 mg/m2 (7pts) and 40 mg/m2 (7pts). Median age was 56 years; 95% of pts had a WHO performance status 0 or 1. The most frequently reported adverse events were nausea in 19 patients (50.0 %), diarrhea in 18 patients (47.4 %), fatigue in 15 patients (39.5 %), and vomiting in 9 patients (23.7 %). Grade 1 and 2 diarrhea, fatigue, nausea and vomiting were suspected to be related to AUY922 at doses ≥ 8 mg/m2. Grade 3 events, including atrial flutter, 1pt, at 22 mg/m2, anorexia, fatigue and diarrhea, 2 pts, at 40 mg/m2, were reported as dose limiting toxicities. Expansion of the 40 mg/m2 cohort was initiated in Dec 2008. The median terminal half life of AUY922 at doses up to 28 mg/m2 was 56 h (24 to 108 h). Pharmacodynamic analyses show dose proportional induction of HSP70 in peripheral blood mononuclear cells by AUY922. Six pts achieved disease stabilization for at least 16 and up to 64 weeks. Conclusions: Single-agent AUY922, administered as a weekly infusion, is well tolerated at doses up to 40 mg/m2. Prolonged disease stabilization was seen in a subset of patients receiving AUY922 across dose levels. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Evaluation of clinically selected patients (pts) with advanced non-small cell lung cancer (NSCLC) recruited in China in a phase III, randomized, open-label, first-line study in Asia of gefitinib (G) versus carboplatin/paclitaxel (C/P) (IPASS)

8041^ Background: The IRESSA Pan Asia Study (IPASS) demonstrated superiority of G vs C/P for progression-free survival (PFS) in 1,217 chemonaïve, never/light ex-smokers with WHO PS 0–2, adenocarcinoma histology and stage IIIB/IV NSCLC. PFS favored C/P initially then G, likely driven by different outcomes according to EGFR mutation (M) status. Planned analyses of pts recruited in China are reported. Methods: 372 pts in China (31% of overall population) were randomized to G 250 mg/day (n=184) or C (AUC 5 or 6)/P (200 mg/m2) (n=188). Primary objective was to assess PFS in ITT population; a treatment by country interaction test (China vs other) was performed. Secondary endpoints were overall survival (OS), objective response rate (ORR, RECIST), QoL (FACT-L, TOI), symptom improvement (LCS) and tolerability. Results: PFS results for pts in China did not significantly differ from other pts (interaction test p=0.4265). G demonstrated numerically longer PFS vs C/P; effect was not constant over time, favoring C/P initially then G. Preliminary OS (28% maturity; follow-up ongoing) was similar for G and C/P. ORR was significantly higher with G (45%) than C/P (30%). QoL improvement rates were higher with G than C/P (FACT-L 44 vs 34%; TOI 45 vs 25%); symptom improvement rates were similar (LCS 48 vs 42%). G had a more favorable tolerability profile than C/P. Conclusions: For pts in China, efficacy and tolerability data were generally consistent with the overall population. G demonstrated improved efficacy (PFS and ORR), similar OS, higher QoL and similar symptom improvement rates and more favorable tolerability profile compared with C/P in chemonaïve, never/light ex-smokers with advanced NSCLC and adenocarcinoma histology. In IPASS, EGFR mutation status appeared to be a strong predictive biomarker for G efficacy compared with C/P. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Phase I study of BAY 73–4506, an inhibitor of oncogenic and angiogenic kinases, in patients with advanced refractory colorectal carcinoma (CRC)

3560^ Background: BAY 73–4506 is a potent inhibitor of the receptor tyrosine kinases (VEGFR, KIT, RET, FGFR and PDGFR) and serine/threonine kinases (RAF and p38MAPK). In in-vivo models, BAY 73–4506 has demonstrated a broad spectrum of antitumor activity. Methods: This phase I study investigated the safety and pharmacokinetic (PK)/pharmacodynamic (PD) profiles of BAY 73–4506, given orally in repeating cycles of 21 days on/7 days off, in patients with refractory CRC. PK assessments were performed on days 1 and 21 of cycle 1. PD markers - including DCE-MRI and plasma levels of VEGF/soluble VEGFR-2 - were assessed at each cycle. Tumor response was evaluated per RECIST. Results: 38 patients with actively progressing CRC were treated with BAY 73–4506 at doses of 60 mg (n = 1), 120 mg (n = 4), 160 mg (n = 26), and 220 mg (n = 7) once daily. Median treatment duration was 56.5 days (range, 7–219 days). Drug-related adverse events (AEs) of all grades reported in >20% of patients were hand-foot skin reaction (HFSR) (61%; CTC 3–4, 32%), fatigue (45%; CTC 3, 11%), hoarseness (24%; CTC 3, 3%), mucositis (24%), diarrhea (24%; CTC 3, 3%), anorexia (24%), and hypertension (21%; CTC 3, 13%). Treatment-related AEs leading to dose reduction, interruption, or discontinuation (in ≥2 of patients) were HFSR (26%), fatigue (18%), thrombopenia (8%), and hypertension (5%). BAY 73–4506 showed a dose-dependent increase in exposure up to 160 mg, at which point a plateau was reached. One of 27 evaluable patients achieved a partial response (4%), 15 had stable disease (SD) at least 7 weeks after the start of treatment (55%), and 6 had SD for more than 23 weeks (22%). Patients had extensive previous antitumor treatment, including bevacizumab (44%) and cetuximab (59%). Decreases in soluble VEGFR-2 levels and iAUC60s of Gd-DTPA by DCE-MRI demonstrated that BAY 73–4506 was active on biologically relevant markers. Conclusions: BAY 73–4506 dosing at 160 mg daily, using a treatment schedule of 21 days on/7 days off was feasible in patients with advanced refractory CRC. Promising clinical activity was shown, with a disease control rate (PR+SD) of 59% in evaluable patients. Mutational analysis of selected genes (KRAS, BRAF) is ongoing. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

A prospective multicenter phase II trial of systemic ADH-1 in combination with melphalan via isolated limb infusion (M-ILI) in patients with advanced extremity melanoma

9025^ Background: ILI with melphalan dosing corrected for ideal body weight (IBW) is a well tolerated treatment for patients with in-transit extremity melanoma with an approximate 30% CR and 44% overall response rate. ADH-1 is a cyclic pentapeptide that disrupts N-cadherin adhesion complexes. ADH-1 when given systemically in a preclinical model with regional melphalan demonstrated synergistic antitumor activity and had minimal toxicity in a Phase I trial with M-ILI. Methods:AJCC stage IIIB or IIIC extremity melanoma patients were treated with 4000mg of ADH-1 administered systemically on Day 1 and 8 in addition to standard dose M-ILI corrected for IBW on Day 1. Drug pK, and N-cadherin IHC staining were performed on pretreatment tumor from all patients. The primary endpoint was response at 12 weeks determined by modified RECIST. Results: 46 patients were enrolled over 15 months at 4 institutions. Thirty-four patients are presently evaluable for 12 week response. In field responses include 14 CRs (41.2%%), 9 PRs (26.5%), 5 SDs (14.7%), and 6 PDs (17.6%). The OR rate was 67.7% and at a median follow-up of 30 weeks, 8 patients have sustained CRs over 6 months. Of 34 patients, 9 have developed disease outside the region of infusion (median time to progression 12 weeks) at median follow-up 36 weeks. N-cadherin was detected in 20 of 25 (80%) pretreatment tumor samples. Grade IV toxicities included CPK elevation (4), neutropenia (1), acute respiratory distress syndrome (1), pneumonitis (1), and pulmonary infiltrate (1). There were no limb losses or compartment syndromes. Conclusions:This study is not only the first prospective multi-center ILI trial but also the first ILI study to incorporate a targeted agent in an attempt to augment anti-tumor responses. The treatment was well tolerated with CR and OR rates that appear to be significantly improved from standard M-ILI alone. Targeting N-cadherin may represent a novel strategy for improving melanoma sensitivity to chemotherapeutic agents and warrants further investigation in a large randomized multi-center trial. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Clinical benefit of bevacizumab (BV) plus first-line docetaxel (D) in elderly patients (pts) with locally recurrent (LR) or metastatic breast cancer (mBC): AVADO study

1094^ Background: In the AVADO study, BV + D confirmed the clinical benefit of combining BV with taxane-based first-line chemotherapy. This analysis evaluated the safety and efficacy of BV + D in pts aged ≥65 years. Methods: Pts with HER2-negative, inoperable, LR or mBC received BV 7.5 or 15mg/kg + D 100mg/m2 or placebo (PL) + D. Pts had no prior chemotherapy for advanced disease, no CNS metastases, ECOG PS 0–1, adequate LVEF. D was administered q3w up to nine cycles, BV/PL q3w until disease progression/unacceptable toxicity. Results: BV + D significantly increased PFS compared with PL + D (BV 7.5: HR = 0.69, p=0.004; BV 15: HR = 0.61, p=0.0001) (Table) (median follow-up 10.2 months). BV significantly increased overall response rate (ORR) compared with PL. In the 127 (17.3%) pts aged ≥65 years, pts had a similar treatment benefit compared to the entire study population. Generally, BV had limited additional impact on the known side effects of D. No grade ≥3 GI perforation, wound-healing complications, CHF or proteinuria were reported. Conclusions: In this retrospective analysis of the AVADO study, addition of BV to D was generally well tolerated in elderly pts with mBC. The magnitude of the benefit in pts aged ≥65 years was similar to that in the overall study population but failed to reach statistical significance, probably due to the small sample size. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Results from panitumumab (pmab) regimen evaluation in colorectal cancer to estimate primary response to treatment (PRECEPT): Second-line treatment with pmab and FOLFIRI by tumor KRAS status

4067^ Background: Pmab, a fully human antibody to the epidermal growth factor receptor (EGFR), is indicated as monotherapy for treatment of metastatic colorectal cancer (mCRC). Mutation status of KRAS in mCRC tumors has recently been shown to predict response to anti-EGFR antibody therapies. The effect of KRAS tumor status on the efficacy of second-line pmab + FOLFIRI was evaluated in this prospective analysis. Methods: Patients (pts) were enrolled in this phase 2, open-label, single-arm study after failure of first-line treatment with oxaliplatin-based chemotherapy + bevacizumab. Pts with unresectable, measurable disease; ECOG status 0/1; with tumor samples available for KRAS testing were eligible. Pts received pmab 6 mg/kg + FOLFIRI Q2W until disease progression or intolerability. Tumor assessments were performed at wks 8, 16, 24, 32, and Q12W thereafter. DNA extracted from fixed tumor sections was used to determine KRAS status by real-time PCR. Efficacy (objective response, progression-free survival [PFS], and overall survival [OS]) and safety were evaluated by KRAS status. Results: In an interim analysis (May 2008) of 115 pts who had received ≥ 1 dose of pmab, 109 pts had known KRAS status (59% had tumors with wild-type [WT] KRAS, 41% had mutant [MT] KRAS tumors), and 102 pts had the opportunity to have their first tumor assessment. Efficacy outcomes by KRAS status are shown ( Table ). Pmab-related AEs were reported in 93% of pts; 87 pts (76%) had ≥ grade 3 AEs (related and unrelated). Most common AEs were skin-related toxicities (86% of pts), diarrhea (72%), and nausea (53%); there was no evidence that incidence of AEs was related to KRAS status. Conclusions: In interim analyses, numerical differences in PFS and OS in favor of pts with WT KRAS were observed. Pmab had a safety profile consistent with other FOLFIRI + pmab trials. Final efficacy and safety data will be presented. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

A randomized, double-blind phase III study of pazopanib in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC)

5021^ Background: Pazopanib, an oral multikinase angiogenesis inhibitor, has shown clinical efficacy in patients (pts) with advanced RCC. In this study (VEG105192), the efficacy and safety of pazopanib was compared with placebo in advanced RCC. Methods: Pts (N = 400 planned) with clear cell advanced RCC and measurable disease with no prior treatment or 1 prior cytokine-based treatment, were stratified and randomized (2:1) to pazopanib 800 mg QD or placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), response rate (RR), and safety. The study had ≥ 90% power to detect an 80% improvement in PFS and a 50% improvement in OS, by stratified log-rank tests with α = 0.025 one-sided. Pts received continuous treatment until disease progression (PD), death or unacceptable toxicity. Upon PD, placebo pts could receive pazopanib via an extension study. Final PFS, RR and safety results are reported here. Results: A total of 233 treatment-naïve and 202 cytokine-pretreated pts were enrolled (290 pazopanib; 145 placebo). Pt characteristics were balanced between the 2 arms. ECOG 0/1 was 42%/58% and 41%/59% for pazopanib and placebo pts, respectively. PFS was significantly prolonged with pazopanib in the overall study population (9.2 vs 4.2 mos; HR: 0.46; 95% CI: 0.34, 0.62; p < 0.0000001), in treatment naïve pts (11.1 vs 2.8 mos; HR: 0.40; 95% CI: 0.27, 0.60; p < 0.0000001), and in cytokine-pretreated pts (7.4 vs 4.2 mos; HR: 0.54; 95% CI: 0.35, 0.84; p < 0.001). RR was 30% with pazopanib (vs 3% with placebo) and median duration of response was 58.7 wks. Median duration of exposure was 7.4 mos (pazopanib) and 3.8 mos (placebo). The majority of adverse events (AEs) were grade 1 or 2. Most common AEs in pazopanib-treated pts were diarrhea (52%; 4% Gr 3/4), hypertension (40%; 4% Gr 3/4), hair color change (38%; <1% Gr 3/4), nausea (26%; <1% Gr 3/4), anorexia (22%; 2% Gr 3/4), and vomiting (21%; 2% Gr 3/4). The most common laboratory abnormality was ALT elevation (53%; 10% Gr 3; 2% Gr 4). Conclusions: Pazopanib monotherapy was well tolerated and demonstrated a significant improvement in PFS and RR compared to placebo. Final OS results are awaited. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Neoadjuvant bevacizumab, oxaliplatin, 5-fluorouracil, and radiation in clinical stage II-III rectal cancer

4105^ Background: This study evaluates induction bevacizumab and FOLFOX followed by concurrent chemoradiotherapy (CRT) with bevacizumab, weekly oxaliplatin, and continuous infusion 5-FU prior to surgical resection of newly-diagnosed Stage II or III rectal cancer. Methods: Eligible patients received one month of induction, biweekly bevacizumab (5mg/kg) and modified FOLFOX6. Patients then received 50.4Gy of radiation and concurrent bevacizumab (5 mg/kg on days 1, 15, and 29), oxaliplatin (50 mg/m2/week for 6 weeks), and 5-FU (200mg/m2/day) as a continuous IV infusion throughout radiation. Due to gastrointestinal toxicity, the oxaliplatin dose was reduced to 40 mg/m2/week. Resection was performed 4 to 8 weeks after the completion of CRT. Adjuvant chemotherapy was started after 4 but less than 12 weeks following surgical resection and consisted of 6 biweekly treatments of modified FOLFOX6 and bevacizumab. Results: Twenty-six eligible patients were treated. The median age was 50. One patient developed a grade 4 arrhythmia during induction chemotherapy and was removed from the study. Of the remaining 25 patients, there were no other grade 3 or 4 toxicities during induction FOLFOX/bevacizumab. Toxicity was more significant during chemoradiation. Any grade 3 toxicity was experienced by 19 of 25 (76%) patients. Grade 3 toxicities included diarrhea (40%), neutropenia (16%), pain (16%), fatigue (8%), nausea (8%), and radiation dermatitis (8%) and bleeding with menstruation (4%). Grade 4 toxicities included neutropenia (4%), sepsis (4%) and nausea/diarrhea (4%). Six of 25 resected patients (24%) had a complete pathologic response. Eight of 25 patients (32%) developed post-operative wound complications including infection/abscess (n=4), fistula (n=2), ischemic colonic reservoir (n=1) and sterile fluid collection (n=1). Nine of 25 (36%) patients developed postoperative wound complications including infection (n=4), delayed healing (n=3), leak/abscess (n=2), sterile fluid collection (n=2), ischemic colonic reservoir (n=1), and fistula (n=1). Conclusions: Concurrent oxaliplatin, bevacizumab, continuous infusion 5-FU and radiation causes significant gastrointestinal toxicity. The pathologic complete response rate of this regimen to similar to other fluorouracil based chemoradiaton regimens. The high incidence of post-operative wound complications is concerning and consistent with other reports utilizing bevacizumab prior to major surgical resections. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Effect of macroscopic vascular invasion (MVI), extrahepatic spread (EHS), and ECOG performance status (ECOG PS) on outcome in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib: Analysis of two phase III, randomized, double-blind trials

4580^ Background: The landmark phase III SHARP trial (Llovet et al, N Engl J Med, 2008) showed that sorafenib is effective and safe for the treatment of advanced HCC. These results were confirmed in an Asian population in the phase III Asia-Pacific (AP) study (Cheng et al, Lancet Oncol, 2009). We compared outcomes of sorafenib treatment in patients enrolled in the SHARP and AP trials with known baseline predictors of poor prognosis. Methods: Patients with advanced, unresectable, measurable HCC, ECOG PS 0–2, Child-Pugh A, and no prior systemic therapy for HCC were randomized to sorafenib 400 mg BID or placebo (SHARP: N=602; AP: N=226). Patients in the AP study had more evolved disease and a predominance of hepatitis B infection. Endpoints included overall survival (OS), disease-control rate (DCR; defined as complete/partial response or stable disease by RECIST, maintained for ≥28 days from first demonstration of response), and safety. Results: Efficacy results are shown in the table . The incidence of grade 3/4 drug-related adverse events (AEs) across subgroups in each study was consistent with the overall population for each study. The most common grade 3/4 AEs in all sorafenib populations were hand-foot skin reaction and diarrhea. Conclusions: Sorafenib is effective and safe for the treatment of advanced HCC in patients globally, irrespective of baseline ECOG PS and presence or absence of MVI and/or EHS. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

A phase Ib/II trial of AMG 655 and panitumumab (pmab) for the treatment (tx) of metastatic colorectal cancer (mCRC): Safety results

4130^ Introduction: Pmab is a fully human antibody targeting the epidermal growth factor receptor that is approved as monotherapy for mCRC in the US, EU, and Canada. AMG 655 is an investigational, fully human agonistic antibody against death receptor 5. This is the first study to evaluate the safety, tolerability, and efficacy of AMG 655 and pmab for the tx of mCRC. Methods: Eligible patients (pts) were ≥ 18 years old, had ECOG status 0–1, radiographic disease progression (PD) during or after tx with fluoropyrimidine, irinotecan, and/or oxaliplatin chemotherapy for mCRC. This is a 2-part study: in part 1 (n∼6–27 pts), the primary endpoint is the incidence of dose-limiting toxicities (DLTs); in part 2 (n∼38–41 pts), the primary endpoint is objective response rate per modified RECIST. Secondary endpoints for both parts include efficacy, pharmacokinetics (PK), and antibody formation. In part 1, pts received pmab 6 mg/kg Q2W plus AMG 655 at a starting dose of 10 mg/kg (evaluation of subsequent doses of 3 mg/kg or 1 mg/kg if needed; 6–9 pts at each dose) by sequential intravenous infusion at week 1 and Q2W thereafter until PD or intolerability. The tolerable dose in part 1 was selected for part 2. Results: We describe here the safety of the first 15 pts (n=5 part 1; n=10 part 2) after ≥ 8 weeks on study. Eight (53%) pts were women, 14 (93%) pts were white, and 9 (60%) pts had ECOG 1. Median (range) age was 61 (38–77) years. All pts received pmab 6 mg/kg and AMG 655 10 mg/kg Q2W. Median (range) follow-up time was 15.4 (9–31) weeks. There were no DLTs in part 1, thus AMG 655 10 mg/kg Q2W was selected for part 2. One (7%) pt had a tx-related adverse event (AE) ≥ grade (gr) 3: gr 3 hypomagnesemia. Tx-emergent Aes ≥ 25% are shown ( Table ). Laboratory values ≥ gr 3: one gr 3 AST and ALT; one gr 3 lipase. From intensive PK samples from the first 6 pts, pmab had no apparent impact on the PK of AMG 655. Conclusions: AMG 655 and pmab can be safely combined in later lines of tx for mCRC. The study is ongoing. Safety results for additional pts will be presented. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Phase I trial of RAD001 (everolimus) plus sunitinib in patients with metastatic renal cell carcinoma

5037^ Background: RAD001 (everolimus) and sunitinib (SUTENT) both have activity in metastatic renal cell carcinoma (mRCC). Combining RAD001 and sunitinib may increase antitumor efficacy by maximizing inhibition of HIF-dependent signaling. The safety and maximum tolerated dose (MTD) of sunitinib in combination with RAD001 was assessed in this phase I trial. Methods:Cohorts of 3–6 patients (pts) with mRCC received sunitinib at 37.5 or 50 mg daily for 4 weeks (wks) followed by 2 wks off with RAD001 administered either daily (2.5 or 5 mg) or weekly (20 or 30 mg). Predetermined dose-limiting toxicities (DLTs) were assessed in the first 6-wk cycle. Serum levels of RAD001 and sunitinib were measured for pts on weekly RAD001. Results: Of 20 pts (median age 62; 13 clear cell (cc) and 7 non-cc RCC) enrolled, 19 are evaluable for DLT including 3 in cohort 1 (2.5 mg RAD001 daily/ 37. 5 mg sunitinib), 2 in cohort 2 (5 mg RAD001 daily/ 37. 5 mg sunitinib), 5 in cohort 3 (20 mg RAD001 weekly/ 37. 5 mg sunitinib; 1 pt too early to evaluate), 6 in cohort 4 (30 mg RAD001 weekly/ 37. 5 mg sunitinib), and 3 in cohort 5 (30 mg RAD001 weekly/ 50 mg sunitinib). On daily RAD001 dosing, 2/2 patients on 5 mg/day experienced grade (G) 3 DLT (thrombocytopenia and mucositis; vomiting). On weekly RAD001 dosing, 2/3 patients on cohort 5 experienced G3 DLT (mucositis; thrombocytopenia with bleeding). 1/6 patients on cohort 4 experienced G3 DLT (febrile neutropenia and mucositis). Therefore, the MTD was cohort 4. However, with chronic treatment, only 1/6 pts at cohort 4 tolerated treatment beyond 4 cycles. Toxicities observed with chronic dosing include: G3 strep viridans endocarditis, G3 gastrointestinal hemorrhage with G4 anemia, and G4 pulmonary embolism. Therefore, we treated 3 more pts at cohort 3. All 6 pts remaining on study, including 2 dose reduced from other cohorts, are on 20 mg RAD001 weekly/ 37. 5 mg sunitinib. 3/5 pts with confirmed partial responses have non-cc RCC (2 chromophobe; 1 papillary). RAD001 blood levels (Cmax and AUC) at 20–30 mg/week were comparable to those seen at 50–70 mg/week in a single agent study. Conclusions: The combination of 20 mg RAD001 weekly/ 37. 5 mg sunitinib is recommended for phase II and shows responses in non-cc RCC. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Randomized, open-label, multicenter phase II study of bevacizumab in combination with carboplatin and paclitaxel in chemotherapy-naive Japanese patients with advanced or recurrent nonsquamous non-small cell lung cancer (NSCLC): JO19907

8036^ Background: Two phase III trials (ECOG 4599 and BO17704) demonstrated that the addition of bevacizumab (Bev) to platinum-based regimens improved overall and/or progression-free survival (PFS) in patients (pts) with advanced non-squamous NSCLC (Sandler et al. NEJM 2006; Manegold et al. ESMO2008). However, no investigation with Bev has been conducted in Japanese NSCLC pts. Methods: This randomized, open-label phase II study compared a 3-weekly regimen of 15mg/kg of Bev plus carboplatin/paclitaxel (CP) versus CP alone. The primary endpoint was PFS; secondary endpoints included overall survival (OS), response rate (RR) and safety. Eligibility criteria: histologically or cytologically documented previously untreated advanced or recurrent non-squamous NSCLC; ECOG PS 0–1; no brain metastases. A size of 180 pts was planned to be randomized to: C AUC=6 and P 200mg/m2 q3 wks for up to 6 cycles plus Bev continued to progression at 15mg/kg q3 wks, or CP alone at the randomization ratio of 2:1. The study was designed to observe a 20% reduction in the risk of a PFS event in the Bev arm compared with control. Results: Between 4/07 and 3/08, 180 pts were accrued. Three pts of them were ineligible and 3 pts were not dosed at all. PFS (as assessed by investigators) and RR were significantly improved. OS is immature due to short duration of follow up. Updated PFS results as assessed by the central review committee and OS data will be provided. No new safety signals for Bev were detected. Conclusions: This is the first study of Bev in Japanese pts with NSCLC. The addition of 15mg/kg of Bev to CP significantly improved PFS and RR. The HR of PFS seemed at least as good as previous trials outside Japan. Safety of Bev was within a range already reported. This study confirms the efficacy and safety of Bev in Japanese pts with NSCLC. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

An analysis of safety in patients (pts) with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) receiving chemotherapy (CT) with or without panitumumab (pmab) in a phase III clinical trial (SPECTRUM)

6050^ Background: The epidermal growth factor receptor (EGFR) is an important target for treatment of patients with SCCHN. Pmab is a fully human monoclonal antibody against EGFR. This study is planned to assess the safety and efficacy of pmab in combination with a standard platinum-based CT regimen for patients with R/M disease. Methods: This ongoing, global, phase III, open-label, randomized (1:1) study is enrolling pts with R/M SCCHN. Pts receive cisplatin 100 mg/m2 IV on day 1 plus 5-FU (1,000 mg/m2) continuous IV daily on days 1–4 ± pmab (9 mg/kg on day 1) every 21 days for up to 6 cycles. Changes to carboplatin (AUC 5) are allowed for specific cisplatin-related toxicities. Pts in the pmab arm without disease progression after 6 cycles may remain on pmab monotherapy until disease progression or intolerability. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, response rate, duration of response, and safety. This study includes multiple planned safety interim analyses conducted by an independent Data Monitoring Committee (DMC). The latest analysis included the first 300 of approximately 650 planned patients. Results: Of 300 pts enrolled, 88% are male; median age is 59 years (range 31–82); ECOG PS 0: 32%, PS 1: 68%. Of the 300 patients, 99% received any study treatment and 76% had ended all CT. Median follow-up time is 13.9 weeks. The rate of any grade 5 treatment-related AE was 3.4%. Adverse events of interest are shown in the Table. Conclusions: After the interim safety analysis of the first 300 pts conducted by the independent DMC, SPECTRUM continues per protocol. Enrollment is estimated to be completed in Feb 2009. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma (HCC): Asia-Pacific (AP) trial subgroup analyses by baseline transaminase (ALT/AST)/α-fetoprotein (AFP) levels

4590^ Background: Results of the phase III, randomized, double blind, placebo-controlled AP trial demonstrated that sorafenib is effective and safe for the treatment of advanced HCC in patients from the AP region (Cheng et al, Lancet Oncol, 2009). Hepatic function influences treatment as a measure of organ damage and tumor stage. We performed subset analyses of the AP study dataset according to baseline hepatic function, as indicated by levels of ALT/AST and AFP. Methods: Patients (N=226) with advanced HCC, ECOG PS 0–2, Child-Pugh class A, and no prior systemic therapy were randomized 2:1 to receive sorafenib 400 mg BID or placebo. Endpoints included overall survival (OS), disease-control rate (DCR; defined as complete/partial response or stable disease by RECIST, maintained for ≥28 days from first demonstration of response), time to progression (TTP) and safety. Patients were grouped by baseline levels of ALT/AST (normal, mild, or moderate) and AFP (normal or abnormal). Results: Median TTP, OS and DCR by subset are shown in the table . The most common grade 3/4 adverse events in the sorafenib populations were hand-foot skin reaction and diarrhea. Conclusions: Sorafenib was effective and safe in patients from the AP region with advanced HCC within a broad range of baseline hepatic enzyme and AFP levels. These results suggest that sorafenib is an effective treatment for HCC, irrespective of baseline ALT/AST or AFP levels. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Chemosensitivity (CS) of patient (pt) breast cancer (BrCa) cells in vitro: Correlation with prior chemotherapy (CT) and implications for personalized treatment planning

e11563^ Background: A predictive BrCa chemosensitivity assay will facilitate individualized treatment. Unlike older assays, the Microculture Kinetic (MiCK) assay measures active apoptosis. In order to determine the in vitro CS of pt BrCa cells, we tested pt tumor cells (tc) in vitro using the MiCK assay. Methods: Tumor excisions or biopsies were sent to a central laboratory, prepared using our previously described MiCK technology (Lab Invest 74: 557, 1996) and tc apoptosis was measured over 48 hours with various drugs. In vitro results were compared to clinical status. CS was measured in kinetic units of apoptosis (KU) with inactive <1.0, low CS 1.0–2.59, moderate CS 2.6–4.2, and high CS >4.2. Physicians (MDs) decided on CT without knowledge of MiCK results. Results: 57 pts were evaluable for MiCK results. CS to drugs for tc from pts with no prior CT was: paclitaxel (P) mean 1.2 KU, cyclophosphamide as 4-hydroxycyclophosphamide (4HC) 2.7, doxorubicin (Dox) 1.8, epirubicin (Epi) 2.1, docetaxel (Doc) 2.0, vinorelbine 0.9, gemcitabine (Gem) 0.7, liposomal D 1.4, carboplatin (Carbo) 1.7, cisplatin (Cis) 2.0, and topotecan 1.2. Combinations tested in some pts showed Carbo-P 2.6 KU and Cis-Gem 2.7. These results were compared to CS of tc from pts with prior CT. CS for pts with prior CT were P 1.8 KU, Doc 1.7, Dox 1.9, Epi 2.9, 4HC 1.1, and Vin 1.2. Although there was no difference between the CS of BrCa cells with or without prior CT for Dox or Epi, CS for 4HC was statistically significantly reduced after prior CT (p<0.0003). Overall, Doc had higher CS than P (p<0.004), Epi higher than Dox (p<0.0001), and 4HC higher than P (p<0.0001) or Carbo (p=0.03). However, in individual pts, P was higher or equal to Doc in 5/18 (28%), Dox higher or equal to Epi in 9/36 (25%), and P higher or equal to 4HC in 5/32 (16%). Conclusions: This indicates that the MiCK assay may be used to evaluate CS of BrCa cells from individual pts. After prior CT, BrCa cells show altered CS profiles, with persistent CS to Dox or Epi but reduced CS to 4HC. These data may be useful to MDs in selecting CT for individual pts. MiCK may also be useful in developing new drugs and new combination therapies. ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

Impact of prior surgical resection with curative intent on the efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma (HCC): Subset analysis of the Asia-Pacific (AP) study

e15518^ Background: The multinational, phase III, randomized, double-blind, placebo-controlled AP study demonstrated that sorafenib is effective and safe for the treatment of advanced HCC in patients from the AP region (Cheng, et al. Lancet Oncol, 2009). Surgical resection with curative intent is a commonly used procedure for the treatment of HCC; however, tumor recurrence occurs in the majority of patients. Hence, it is of interest to analyze the efficacy and safety of sorafenib in patients who had undergone prior partial hepatectomy. Methods: Patients (N=226) with advanced HCC, ECOG PS 0–2, Child-Pugh class A, and no prior systemic therapy were randomized 2:1 to receive either sorafenib 400 mg BID or placebo. End points included overall survival (OS), disease-control rate (DCR; defined as complete/partial response or stable disease by RECIST, maintained for ≥28 d from first demonstration of response), time-to-progression (TTP), and safety. Results: Of 226 patients enrolled, 70 had previously undergone partial hepatectomy. Median TTP, OS, and DCR by subset are shown in the table. The safety profile of sorafenib in patients with and without prior hepatectomy was similar to that reported for the total study population. The most common grade 3/4 adverse events in the sorafenib groups were hand-foot skin reaction and diarrhea. Conclusions: Sorafenib was safe for the treatment of advanced HCC in patients from the AP region, whether or not they had undergone prior surgical resection. Sorafenib treatment resulted in similar TTP in patients with and without a history of prior partial hepatectomy, and the magnitude of TTP was similar in both groups to that in the overall population. Due to small sample size, further study is warranted. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .