ASCO's Policy Research Articles

Social Determinants of Health and Cancer Care: An ASCO Policy Statement

(Abstracted from JCA Oncol Pract 2024;20(5):621–630) Factors that affect access to health care and represent conditions out of an individual’s control are collectively known as social determinants of health (SDOHs); health-related social needs (HRSNs) are related to these, being unmet needs that affect health and health care. In the United States, disparities in health care that are related to both SDOHs and HRSNs are prevalent despite years of research and efforts to minimize them.

Global Equity in Clinical Trials: An ASCO Policy Statement.

ASCO is a global professional society representing more than 50,000 physicians, other health care professionals, and advocates in over 100 countries specializing in cancer treatment, diagnosis, prevention, and advocacy. ASCO strives, through research, education, and promotion of the highest quality of patient care, to create a world where cancer is prevented or cured, and every survivor is healthy. In this pursuit, health equity remains the guiding institutional principle that applies to all its activities across the cancer care continuum. This ASCO policy statement emphasizes the urgent need for global equity in clinical trials, aiming to enhance access and representation in cancer research as it not only improves cancer outcomes but also upholds principles of fairness and justice in health care.

Social Determinants of Health and Cancer Care: An ASCO Policy Statement.

ASCO's new policy statement on SDOH supports practices that sustain and advance cancer health equity.

ASCO Policy Statement on Biosimilar and Interchangeable Products in Oncology.

As the voice of cancer care clinicians and the patients they serve, ASCO has taken steps to elevate awareness about biosimilar products and their use in oncology. In 2018, ASCO released its Statement on Biosimilars in Oncology which was subsequently published in the Journal of Clinical Oncology to serve as an educational tool which highlighted and provided guidance on several topical areas surrounding biosimilars. At the time of its publication, the US Food and Drug Administration (FDA) had approved eight biosimilar products for use in the United States, including one product for use as a supportive care agent in the cancer setting and two products for use in the treatment for cancer. This number has risen dramatically (40 approvals), with a total of 22 cancer or cancer-related biosimilar products approved since 2015. Recently, the FDA also approved the four interchangeable biosimilar products for diabetes, certain inflammatory diseases, and certain ophthalmic diseases. Given the current market dynamics and the regulatory landscape, this ASCO manuscript now seeks to propose several policy recommendations across the scope of value, interchangeability, clinician barriers, and patient education and access. This policy statement is intended to guide ASCO's future activities and strategies and serves to affirm our commitment to providing education to the oncology community on the use of biosimilars in the cancer setting.

Responding to the opioid crisis in a manner that respects oncology patients: A single institution experience writing policy to promote safe opioid use.

132 Background: The current opioid crisis has had wide ranging implications across medicine and in particular oncology practice. Opioids have been used for centuries for their analgesic properties. As physicians and historians are aware, the abuse potential of opioids is significant. Despite this, a dramatic shift in medical education in the late 1990s and early 2000s and aggressive marketing and manufacture of opioids has led to widespread opioid misuse and abuse. Therefore, a slew of regulations has been put into effect within a brief period of time. Among practitioners, the oncologist holds a unique and arguably more challenging role, caring not only for those with acute cancer-related pain or those at the end of life, but also for cancer survivors or those who live with their cancer as a chronic condition. ASCO has put forth comprehensive guidelines for the safe use and monitoring of opioids. The ASCO policy statement also highlights the significant barriers that oncology patients face, thereby maintaining a focus on the unique needs of this patient population. Methods: The Lifespan Cancer Institute is an academic practice and writes approximately 880 opioid prescriptions each month with approximately 15% being new prescriptions. Our Multidisciplinary Quality Team implemented a safe opioid prescribing initiative including patient education sheets, an electronic patient-provider treatment agreement, and an electronic template for provider documentation. Our palliative care team monitors pain scores. Results: During month one, 16% of patients newly prescribed an opioid had a completed patient-provider treatment agreement. For the second month, the number of completed agreements increased to 29%. Conclusions: Given the prevalence of opioid misuse, there is a growing overlap between oncology patients and those with opioid misuse disorder. Given high levels of psychological distress, the cancer patient is at risk for opioid misuse. Furthermore, oncology patients can be victims of diversion. Our responsibility is to screen and educate patients on the risk of opioid addiction and diversion while providing compassionate palliative care.

Addressing Financial Barriers to Patient Participation in Clinical Trials: ASCO Policy Statement.

Research conducted through clinical trials is essential for evaluating new treatment modalities, establishing new standards of cancer care, and ultimately improving and prolonging the lives of patients with cancer. However, participation in trials has been low, and this is attributable to various factors including patient financial barriers. Such financial barriers include the rising cost of cancer care; a lack of transparency in coverage policy; and the perception of ethical, compliance, or institutional impediments to patient financial support. ASCO convened a roundtable discussion with a variety of stakeholders to define the scope of the problem, as well as to identify clinical practice and policy solutions applicable at the institutional and system-wide levels. This statement summarizes key discussions from the ASCO Roundtable, as well as findings from the literature, and provides ASCO's recommendations for overcoming financial barriers that may otherwise prevent participation in clinical trials. These recommendations broadly address the following key areas: (1) improving the policy environment for coverage of clinical trials; (2) facilitating transparency among providers, patients, and payers for trial-related out-of-pocket costs; (3) refuting the specter of inducement to enable targeted financial support for patients; and (4) improving the available data on costs of cancer clinical trials.

Therapy of relapsed/refractory metastatic triple-negative breast cancer (mTNBC) with an anti-Trop-2-SN-38 antibody-drug conjugate (ADC), sacituzumab govitecan (IMMU-132): Phase II results.

LBA509 Notice of Retraction: “Therapy of relapsed/refractory metastatic triple-negative breast cancer (mTNBC) with an anti-Trop-2-SN-38 antibody-drug conjugate (ADC), sacituzumab govitecan (IMMU-132): Phase II results.” ASCO's Confidentiality Policy requires that abstracts be considered confidential and embargoed from the time of submission until the findings have been publicly released in conjunction with the ASCO Annual Meeting. Abstract LBA509, published in the 2016 ASCO Annual Meeting Proceedings Part II, violated this policy and was retracted from publication and presentation at the 2016 ASCO Annual Meeting.

Integrating outpatient palliative care into a metastatic breast oncology clinic.

154 Background: The Advanced Breast Cancer (ABC) program at UCSF aims to improve metastatic breast cancer outcomes through early integration of palliative and oncologic care. Oncologists now routinely refer stage 4 patients to a palliative care physician and social worker. Thus this initiative translates ASCO policy recommendations into clinical practice. We report early results from our development, implementation, and evaluation of this novel program. Methods: To evaluate ABC, we used the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation and Maintenance), and Rogers’ Diffusion of Innovations theory. Results: Reach: From 10/2014 to 6/2015, 43 women participated out of 64 invited. Decliners’ main reason for refusal was to avoid additional appointments. Effectiveness: 36 patients reported improvements in 13 of 15 quality criteria, including care coordination, emotional support, and propensity to recommend the program. 34 patients responded to ESAS, QUAL-E and Steinhauser Spiritualty Screen questionnaires, with improvement in 10 out of 14 outcomes at 1-2 month follow-up. Improvements included reduction of anxiety, improved quality of life, and decreased nausea. Adoption: Early integration of palliative care is complex and requires additional coordination among busy clinicians. To address this, we embedded a palliative care physician in the oncology clinic two half-days per week; relied on an oncology fellow to facilitate ongoing cross-disciplinary collaboration; and leveraged the program coordinator’s capacity for following up on both project and patient issues. We also instituted a monthly team meeting to review patient cases. Implementation: Overall, our program design succeeded. Challenges included how to best communicate about patient prognosis and reason for referral. We also struggled to determine what patient eligibility criteria should trigger a referral. Maintenance: The program is currently sustained by grants and intramural cancer center funding. We are seeking continued investment. Conclusions: The ABC program demonstrates that early integration of palliative and oncologic care is feasible and associated with the psychosocial benefits previously found in efficacy studies.

Effective complementary ASCO policy and day to day decision support strategies optimize anti-emetic choices.

9630 Background: Emetogenicity is a common reason for patients forgoing effective chemotherapy. ASCO, in its 2013 Top Five list, recommends against overuse of antiemetics and for the use of cost-ef...

Phase II study of biweekly dose-intense docetaxel plus gemcitabine (GEM/DOC) in patients with recurrent locoregional or metastatic head and neck squamous cell carcinoma.

5534 Notice of Retraction: "Phase II study of biweekly dose-intense docetaxel plus gemcitabine (GEM/DOC) in patients with recurrent locoregional or metastatic head and neck squamous cell carcinoma." ASCO's Confidentiality Policy requires that abstracts be considered confidential and embargoed from the time of submission until the findings have been publicly released in conjunction with the ASCO Annual Meeting. Abstract 5534, published in the 2012 Annual Meeting Proceedings Part I, a supplement to the Journal of Clinical Oncology, violated this policy and has been retracted from publication and presentation at the 2012 ASCO Annual Meeting. Background: Patients with metastatic head and neck squamous cell carcinoma (HNSCC) have a poor prognosis, limited treatment options, and median survival of 6 to 9 months. Docetaxel and gemcitabine have both shown activity in HNSCC. The optimal combination, dosing, and scheduling of both drugs is, however, unknown. Thus, we investigated the efficacy and safety of biweekly dose intense GEM/DOC in patients with recurrent locoregional or metastatic HNSCC. Methods: An open-label, single-institution, single-arm, phase II study was conducted for patients who were previously treated with no more than two cytotoxic regimens. The patients received docetaxel (60 mg/m2IV) and gemcitabine (3000 mg/m2 IV) on day 1. The treatments were repeated every 14 days (one cycle), until disease progression or unacceptable toxicity. The primary end point was response rate. RECIST-defined response was evaluated every 4 cycles and toxicities were evaluated at each cycle. Results: A total of 36 patients were enrolled (M:F 26:10; median age (range), 60 years (46-79); performance status 0-1) , 29 of whom were response-evaluable. The patients received a median of 4 cycles (range 0-24). Of these 29 patients, none achieved complete response (CR) and 6 demonstrated a partial response (PR). Thus, the overall response rate was 21% (95% confidence interval [CI], 0.10 – 0.38). Ten patients had stable disease (SD), resulting in tumor control (CR or PR or SD) in 16 of 29 patients (55%), whereas 13 patients (45%) had disease progression. The median response duration was 3.2 months (80% CI: 2.0 – 6.1 months). For all 36 patients, the median overall survival was 4.2 months (95% CI: 2.4 – 7.0 months). Myelosuppression was the most common adverse event. Grade 3-4 neutropenia and anemia were observed in 10 (30%) and 13 (39%) patients, respectively. None of these patients, however, had febrile neutropenia or bleeding events, and there were no treatment-related deaths. Conclusions: The combination of biweekly dose intense GEM/DOC was tolerable and active regimen in patients with recurrent locoregional or metastatic HNSCC. Our findings warrant further investigation in a larger patient population.

The NCI Community Cancer Centers Program (NCCCP): A model for reducing cancer health care disparities.

6086 Background: In 2007, NCI launched the NCCCP, a public-private partnership with 16 community hospital cancer centers in 14 states, to explore methods to improve patient access to advanced cancer care in the community. With 40% of its NCI funding directed to reduce disparities across the cancer continuum, the NCCCP aims to: 1) Enhance access to care; 2) Improve quality of care; and 3) Increase clinical trials accrual. This approach supports priorities in the 2009 ASCO Policy Statement: Disparities in Cancer Care. Methods: A disparities workplan was developed to support the three aims. NCI and the sites worked as a learning collaborative to develop strategies and metrics for: race and ethnicity data tracking; near real-time reporting of adherence to Commission on Cancer (CoC) treatment quality measures; community outreach and patient navigation to increase cancer screening; and improved clinical trial underserved accrual. The tools and resources supporting these efforts will be discussed. ( http://ncccp.cancer.gov/About/Progress.htm ). Results: Evaluation of the 3 year pilot shows improvement for underserved populations: Concordance with CoC treatment quality measures for radiation therapy for breast conserving surgery among Medicaid patients improved from 59.5 percent to 84.8 percent (p<.05). Increased community screening events (from 992 to 1,585) and community partnerships focused on underserved populations (from 78 to 195). Increased accrual to NCI trials (minority accrual from 82 to 151 and elderly from 200 to 641). Conclusions: To be effective in reducing healthcare disparities, a multi-level approach is needed. This includes having: organizations which demonstrate a strong community-oriented mission; commitment by hospital management; engagement of private practice physicians; targeted training of staff; use of standardized data collection and metrics; involvement of strategic partners with aligned goals at the national and local level; support by relevant NCI experts; and sharing best practices across a learning collaborative. The NCCCP disparities model was used in a variety of community settings targeting different underserved populations and has demonstrated effect in care in the respective communities.

A phase III study (EMBRACE) of eribulin mesylate versus treatment of physician's choice in patients with locally recurrent or metastatic breast cancer previously treated with an anthracycline and a taxane.

CRA1004^ Background: Eribulin mesylate (E7389; E) is a nontaxane microtubule dynamics inhibitor with a novel mode of action. This study is the first to compare overall survival (OS) with this new chemotherapeutic (CT) agent to real-life choices in heavily pretreated patients (pts) with metastatic breast cancer (MBC). Methods: Women with locally recurrent or MBC were enrolled in this phase III open-label, randomized, multicenter study. Pts had received 2-5 prior CT (≥2 for advanced disease), including an anthracycline and a taxane, unless contraindicated. Pts were randomized 2:1 to E 1.4 mg/m2 2-5 min IV bolus on days 1 and 8 of a 21-day cycle or treatment of physician's choice (TPC). TPC was any monotherapy (cytotoxic, hormonal, biologic) or supportive care only. The primary endpoint was OS; secondary endpoints were objective response rate (ORR), and progression-free survival (PFS) by independent review, and duration of response (DOR). Safety and tolerability were assessed. Data are from the final analysis after 422 deaths. Results: 762 pts were treated (508 E, 254 TPC). Median age was 55.2 (range 27-85), 16% were HER2-positive, 19% triple-negative, 73% received prior capecitabine, median no. of prior CT was 4. Median OS was 13.1 months (mo) for E vs. 10.7 mo for TPC, p=0.04 (primary analysis, stratified log rank test; HR 0.81; 95% CI 0.66, 0.99). Median PFS was 3.7 mo for E and 2.3 mo for TPC p=0.09 (HR 0.85; 95% CI 0.70, 1.03). ORR was 12% (0.4% complete response [CR], 11.5% partial response [PR]) for E and 5% (0 CR; 5% PR) for TPC, p=0.005. Median DOR was 4.1 mo for E (56 responders) vs. 6.7 mo for TPC (11 responders). Grade [G] 3/4 treatment-related adverse events (AEs) of interest for E were asthenia/fatigue (7.6%), neutropenia (44%), peripheral neuropathy (8.4%). 10% of pts experienced treatment-related serious AEs (12% E, 7% TPC). Conclusions: The study met its primary endpoint with a significant improvement in OS by a median of 2.5 mo with E vs. TPC. E demonstrated a manageable tolerability profile, acceptable for a CT agent used as monotherapy in this late-line setting. [Table: see text] 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 2010 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 safety and pharmacology study of the EpCAM/CD3-bispecific BiTE antibody MT110 in patients with metastatic colorectal, gastric, or lung cancer.

2573^ Background: MT110 is a bispecific antibody construct (BiTE) binding to epithelial cell adhesion molecule (EpCAM) expressed on most solid cancers, and to CD3 on T cells. MT110 has shown remarkable antitumor activity in preclinical solid tumor xenograft models. For non-Hodgkin's lymphoma and ALL the CD19-specific BiTE antibody blinatumomab has proven to be highly effective in phase I and II clinical testing. Methods: This phase I study evaluates safety, tolerability, pharmacokinetics, and antitumor activity of MT110 in patients (pts) with advanced solid tumors widely expressing EpCAM. A dose escalation with 3-6 pts per cohort is used to determine maximum tolerated dose (MTD) and dose- limiting toxicities (DLT). Starting dose was 1 μ g/d given by continuous i.v. infusion for at least one 28-day cycle. Results: As of Jan 2010, a total of 23 pts (4 gastric cancer, 16 CRC, 1 SCLC, 2 NSCLC; age ranging from 45 to 85 years, 65% of pts with at least 3 lines of previous chemotherapies) have been treated with MT110 in 6 cohorts up to 24 μ g/d. Overall, MT110 was well tolerated with only few and mild clinical adverse events and pyrexia being the only event reported in more than 2 pts. Liver enzyme elevations caused DLTs in 3 patients at 1, 10, and 24 μ g/d, but were fully reversible. Low-dose MT110 pretreatment partially mitigated the increases in liver enzymes. None of the patients who received a second or subsequent treatment cycles showed an increase in transaminases. As also observed with blinatumomab, MT110 caused a rapid and transient redistribution of peripheral lymphocytes. Mean steady-state serum concentrations of MT110 were dose-dependent reaching up to 1.4 ng/ml at 24 μ g/d. None of the pts developed antibodies against MT110. Disease stabilization according to RECIST was found in 7 of 19 evaluable pts, with a median duration of 91 days (range 56-150 days). Expansion of CD8+ T-cell counts by more than 2-fold over baseline was observed in 5 out of 22 pts. Conclusions: Early signs of biological activity have been observed at clinically well tolerated doses of MT110 in this first-in-human clinical trial. Evaluation of T cell-engaging BiTE antibody MT110 at higher doses is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Genomic Health, sanofi-aventis Amgen, Genomic Health, sanofi-aventis 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 2010 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.

Chemoimmunotherapy with ofatumumab, fludarabine, and cyclophosphamide (O-FC) in previously untreated patients with chronic lymphocytic leukemia (CLL).

6520^ Background: Ofatumumab, a human monoclonal antibody targeting a unique epitope encompassing both large- and small-loop of CD20, demonstrated high overall response rates (ORR) in a pivotal study in refractory CLL. We conducted an international, randomized, phase II trial to assess efficacy and safety of two dose levels of O-FC in previously untreated patients (pts) with CLL. Methods: Pts with active CLL were randomized to ofatumumab 500 mg (Group A) or 1,000 mg (Group B) Day 1, with fludarabine 25 mg/m2 and cyclophosphamide 250 mg/m2 Days 2–4, Course 1; Days 1–3, Courses 2–6; every 4 weeks for 6 courses. First ofatumumab dose was 300 mg. The primary endpoint was complete response (CR) rate (1996 NCI-WG criteria) evaluated by an Independent Review Committee during treatment until 3 months after last dose. Results: 61 pts were randomized (Group A, n=31; Group B, n=30). CR rate was 32% and 50% for Group A and B; ORR was 77% and 73%, respectively. Responses by baseline and treatment parameters are shown (Table). Short median follow-up (8 months) currently does not permit analyses of time-to-event endpoints. Ofatumumab Cmax (426 vs. 201 mg/L) and Cmin (60 vs. 20 mg/L) at 6th infusion were higher in Group B vs. Group A. Based on exploratory univariable regression analyses, lower β2-microglobulin (as continuous variable), completion of 6 courses of O-FC, and higher ofatumumab Cmin prior to last infusion were significantly correlated with increased likelihood for response including CR, and decreased risk for progression. Additional pharmacokinetic analyses are ongoing. Conclusions: O-FC is highly active in previously untreated pts with CLL. β2-microglobulin level, number of O-FC courses completed, and Cmin prior to last course correlated with outcomes with O-FC Parameters N % CR % ORR All pts 61 41 75 Age <65 50 44 76 ≥65 yrs 11 27 73 ALC <30 × 109/L 11 64 82 ≥30 × 109/L 50 36 74 Lymph nodes ≤5 cm 51 39 78 >5 cm 10 50 60 Rai stage 0-II 33 36 73 III- IV 28 46 79 β2-M <4 mg/L 32 53 84 ≥4 mg/L 28 29 68 CD38+ <30% 48 44 77 ≥30% 12 33 67 IGHV mutated 28 46 75 IGHV unmutated 25 36 84 17p del 8 13 63 11q del 10 40 70 Trisomy 12q 9 56 56 No FISH abn. 7 71 100 13q del (sole) 25 32 80 No. of O-FC courses received: 6 39 56 92 4–5 9 33 78 1–3 13 0 23 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Genomic Health, sanofi-aventis Amgen, Genomic Health, sanofi-aventis 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 2010 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.

Safety and efficacy of presurgical neoadjuvant low-dose temozolomide in glioma patients.

e12510^ Background: Temozolomide (TMZ) has become the chemotherapy of choice for patients with malignant glioma. Activity has been demonstrated in a range of tumor histologies and tumor grades. A possible mechanism of resistance is the presence of high methylguanine methyltransferase (MGMT) in the tumor leading to reduced cytotoxic activity of TMZ. Experimental models have shown that continuous exposure to TMZ can deplete MGMT activity and possibly restore sensitivity to TMZ. Presurgical (neoadjuvant) treatment with TMZ may be beneficial in reducing MGMT activity and improving patient outcome. Methods: This phase II study assessed the safety and efficacy of TMZ at a dose of 75 mg/m2 administered daily for 14 days prior to surgery for treatment-naïve glioma. Results: 40 patients, median age 47 (18-76) with surgically resectable tumors were enrolled from December 2006 to December 2009. Ninteen male and 21 female patients self-selected to TMZ (34) or control (6) cohorts. Tumors were: oligodendrogliomas 37%, astrocytomas 28%, glioblastoma multiforme 18% and Mixed tumors 17%; 50% were high grade tumors. A majority of patients 63% had a partial resection; the remaining had a complete resection. MGMT promoter methylation was performed on fresh frozen tissue and significant levels were found in 60% of patients. All patients in the TMZ cohort completed 2 weeks of therapy. Treatment was well tolerated and toxicities were rare with 60% of patients not reporting any treatment related adverse events. Lymphopenia was the only grade 3 toxicity observed in TMZ treated patients. No grade 4 toxicities were reported. At histological examination, an increased number of apoptotic cells were observed in tumor from TMZ patients. Conclusions: Presurgical neoadjuvant TMZ is well tolerated with few toxicities observed. The increased number of apoptotic cells demonstrated action of TMZ on the tumors and suggest tumor cytoreduction could be performed before surgery. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough Canada/Merck Schering-Plough Canada/Merck Merck Schering-Plough Canada/Merck Schering-Plough Canada/Merck 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 2010 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 II study of biweekly temozolomide plus bevacizumab for adult patients with recurrent glioblastoma multiforme.

e12554^ Background: Glioblastoma multiforme (GBM) accounts for half of all primary brain tumors and despite decades of research, median survival is about 8-12 months. Temozolomide (TMZ) is an alkalating agent which is approved as a first-line therapy for GBM. Bevacizumab (BEV) is a monoclonal antibody which targets vascular endothelial growth factor and is approved for the treatment of recurrent GBM. The combination of BEV and standard dosing of TMZ may not increase survival above the use of TMZ alone. Alternate dosing of TMZ has been shown to further increase survival in a sub-set of patients. The purpose of this study is to determine the 6-month progression-free survival of patients with recurrent GBM treated with BEV plus biweekly dosing of TMZ. Secondary end-points include radiographic response, evaluation of toxicity, analysis of tumor DNA (MGMT), and functional assessment of cancer therapy for brain tumors (FACT-Br). Methods: Patients with recurrent GBM were treated with BEV 10 mg/kg in combination with TMZ 100 units/m2 every 2 weeks. Complete patient evaluations were repeated every 4 weeks and MRI scans were repeated every 8 weeks. FACT-Br questionnaires were completed every 8 weeks. Results: Accrual goal is 30 subjects; preliminary data is presented. 5 patients have been accrued to this study thus far. 4 patients are actively enrolled in the study. One patient exited after the first cycle of therapy due to progressive disease, the other four have had partial radiographic responses. One patient has been progression-free for > 7 months; the remainder are currently progression-free after 2 cycles. To date there have been no grade 4 toxicities. The following treatment-emergent grade 3 adverse events have been observed: encephalopathy (epileptic), pulmonary emboli and fatigue. Of these, only pulmonary emboli and fatigue were considered possibly drug-associated. Methylation of MGMT gene was NOT detected in any of the 5 subjects. Conclusions: We conclude that the combination of bevacizumab and temozolomide given bi-monthly is well tolerated and may have efficacy in the treatment of recurrent glioblastoma multiforme. Added safety and efficacy data will be reported as this phase II study progresses. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech, Schering-Plough Genentech, Schering-Plough Genentech 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 2010 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.

Everolimus in combination with weekly paclitaxel and trastuzumab in patients (pts) with HER2-overexpressing metastatic breast cancer (MBC) with prior resistance to trastuzumab and taxanes: A multicenter phase II clinical trial.

1013^ Background: Resistance to trastuzumab (H) may be associated with deregulation of PTEN or mutations in PI3K/AKT pathway. Preclinically, everolimus (E), an oral inhibitor of mTOR, enhances activity, reverses resistance to H and demonstrates synergistic activity with paclitaxel (T). The objective of this phase II study was to evaluate the efficacy of E combined with T and H in heavily pretreated HER2-positive MBC pts. Methods: A multicenter, Novartis sponsored, phase II trial was conducted using: T 80mg/m2, IV on days 1, 8 and 15 q4w; H 4mg/kg IV loading dose, then weekly 2mg/kg; E daily 10mg in patients whose disease is resistant to both H (progression on or within 3 months of the end of H therapy for metastatic cancer or within 12 months after the end of neoadjuvant or adjuvant H) and taxanes (progression on or within 4 months of the end of taxane therapy for metastatic cancer or within 12 months after the end of neoadjuvant or adjuvant therapy.) Treatment continued until progression or unacceptable toxicity. Results: The study completed enrollment (n=55). Analyses were performed on 37 evaluable pts. Median treatment duration is 12 weeks (2-43) with19 pts still on treatment and 6 beyond 6 cycles. Pt characteristics were median age 56 y; visceral disease in 33 pts (89%) with lung and liver involvement in 18 pts (49%) and 21 pts (57%), respectively; median no. of prior chemo lines for metastatic disease 3 (range 0-8); prior anthracyclines in 25 pts (68%); prior lapatinib in 23 pts (62%). Twenty-five pts were evaluable for efficacy. We observed 5 (20%) confirmed PRs, 14 (56%) SDs and 6 (24%) PDs. Treatment was well tolerated. G3-4 neutropenia occurred in 12 pts (32%) with 1 case of febrile neutropenia, G3 stomatitis in 5 pts (13%) and G3 asthenia/fatigue in 2 pts (5%). Conclusions: These preliminary results confirm a previous phase I study showing that E in combination with T and H has an acceptable safety profile and promising anticancer activity in HER2-positive MBC pts pretreated with trastuzumab and taxanes. Updated safety, efficacy, and PFS results will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis, Pfizer Novartis Novartis, Pfizer Genentech, Novartis 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 2010 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 phase III study of panitumumab (pmab) with FOLFOX4 compared to FOLFOX4 alone as first-line treatment (tx) for metastatic colorectal cancer (mCRC): PRIME trial analysis by epidermal growth factor receptor (EGFR) tumor staining.

3566^ Background: This study evaluated the efficacy and safety of pmab + FOLFOX4 versus FOLFOX4 alone as first-line tx for mCRC by tumor KRAS status; analyses by EGFR staining were also performed. Methods: Pts who received no prior chemotherapy for mCRC and no prior oxaliplatin were randomized 1:1 to pmab 6.0 mg/kg Q2W+FOLFOX4 (Arm 1) or FOLFOX4 alone (Arm 2). The primary endpoint was progression-free survival (PFS); overall survival (OS) was secondary. PFS and OS were prospectively analyzed according to KRAS status. Using the Dako EGFR pharmDx immunohistochemistry kit, tumor tissue sectioned within 2 months prior to testing was evaluated for EGFR staining. EGFR results were not required for study entry. Results: 1,183 pts were randomized. Demographics and baseline characteristics were generally balanced. 1,096 pts (93%) had KRAS results. For WT KRAS, median PFS was 9.6 mos for Arm 1 and 8.0 mos for Arm 2; median OS was 23.9 mos for Arm 1 and 19.7 mos for Arm 2. 813 (69%) pts had EGFR results. The most common reason for no EGFR result was tissue section ≥2 months old. Of 479 WT KRAS pts with EGFR results, 326 (68%) were EGFR+. The Table shows the treatment effect within the subpopulations by EGFR staining. No treatment effect by EGFR staining was observed in a stratified multivariate Cox model evaluating the predictive effect of EGFR parameters on PFS (p = 0.89) and OS (p = 0.43) in KRAS WT pts. Except for known toxicities associated with anti-EGFR tx adverse event rates were generally comparable across arms. Conclusions: When added to FOLFOX for first-line mCRC tx, pmab significantly improves PFS and is well tolerated in pts with WT KRAS. A consistent effect of pmab on PFS and OS was observed in both EGFR+ and EGFR- subsets. Further results by EGFR staining parameters will be presented. Efficacy by EGFR membrane staining-WT KRAS WT KRAS N = 656 EGFR evaluable WT KRAS N = 479 HR (95% CI) p value HR (95% CI) EGFR+ HR (95% CI) EGFR- PFS* 0.80 0.77 0.80 Pmab FOLFOX : FOLFOX (0.66-0.97) 0.02 (0.58-1.03) (0.53-1.21) OS 0.83 0.77 0.64 Pmab FOLFOX : FOLFOX (0.67- 1.02) 0.07 (0.52-1.13) (0.34-1.18) * By blinded central review. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen, AstraZeneca, Celgene, Fresenius Biotech, Merck Serono, Roche, sanofi-aventis Amgen Amgen, Merck AG, Merck Serono, sanofiaventis Amgen, Merck AG, Merck Serono, Pfizer Amgen 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 2010 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 II study of BIBW 2992 in patients with adenocarcinoma of the lung and activating EGFR mutations (LUX-Lung 2).

7521^ Background: NSCLC patients whose tumors harbor epidermal growth factor receptor EGFR/HER1 mutations represent a unique subpopulation with unparalleled responsiveness to EGFR tyrosine kinase inhibitors. A phase II study of BIBW 2992 – an oral, novel, potent irreversible inhibitor of EGFR and human HER2 – has completed accrual in Taiwan and the US. Methods: Patients with a stage IIIB/IV lung adenocarcinoma, EGFR mutations in exons 18–21 (by direct sequencing), chemo-naïve or with progressive disease following first-line cytotoxic chemotherapy, measurable disease, and ECOG PS 0–2 received 50 mg or 40 mg BIBW 2992 qd until progression. Response was assessed at 4, 8 and 12 weeks, and at 8-weekly intervals thereafter; images were centrally reviewed. Analysis included primary endpoint objective response rate (ORR) and secondary endpoint progression-free survival (PFS). Results: 444 patients were tested for EGFR mutations and 129 received treatment. Tumor size reduction was seen in 90% of patients. ORR and disease control rate (DCR) was 62% and 94%, respectively, for del19; 52% and 85% for L858R; and 43% and 78% for other mutations based on investigator assessment. L858R mutation was seen in 54 (42%), del19 in 52 (40%) and other mutations in 23 (18%) patients. Median PFS was estimated to be 12 months (95% CI: 10–19.2) for the overall group, 12 months (95% CI: 10–19.2) in del19, 16.3 months (95% CI:10–Inf) in L858R, and 15.6 months (95% CI:10–19.2) when combined. The most common drug-related adverse events (AEs) were diarrhea and rash/acne, as reported in 95% of patients each and were Grade 3 in 18% and 19% of patients, respectively. No Grade 4 cases were reported for these events. Conclusions: Administration of BIBW 2992 resulted in a high ORR, DCR and PFS in NSCLC patients with EGFR mutations. Gastrointestinal and skin disorders were the most frequently observed AEs and were manageable with adequate supportive care and dose reduction. Updated response and PFS data based on independent imaging review will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Boehringer Ingelheim Boehringer Ingelheim 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 2010 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.

Sorafenib (SOR) or placebo (PL) in combination with transarterial chemoembolization (TACE) for intermediate-stage hepatocellular carcinoma (SPACE).

TPS178^ Background: SOR acts via antiangiogenesis and inhibition of tumor cell proliferation, and has proven efficacy in advanced hepatocellular carcinoma (HCC). It is relevant to assess whether SOR combined with TACE improves clinical outcomes compared with TACE alone. The phase II SPACE study is being conducted in North America, Europe, and the Asia-Pacific region to evaluate the efficacy and safety of TACE (using doxorubicin-eluting beads) plus either SOR or PL in patients (pts) with intermediate-stage HCC (BCLC B). Methods: SPACE is a multinational, randomized, double-blind, PL-controlled study. Pts aged ≥18 years diagnosed with intermediate-stage HCC (BCLC B; defined as the presence of asymptomatic, unresectable, multinodular tumors without vascular invasion or extrahepatic spread) are eligible if they have Child-Pugh (CP) class A status without ascites; ECOG PS of 0; ≥1 unidimensional lesion measurable according to RECIST; and adequate bone marrow, liver, and renal function. Exclusion criteria include diffuse HCC or vascular invasion (including segmental portal obstruction) and/or extrahepatic spread; advanced liver disease (defined as CP class B/C, active gastrointestinal bleeding, and/or encephalopathy); contraindication to TACE; history of a target lesion treated previously with local therapy; any locoregional therapy ongoing or completed <4 weeks prior to baseline; and history of ≥grade 2 adverse event with any prior local treatment. Eligible pts undergoing TACE with doxorubicin-eluting beads (loaded with 150 mg doxorubicin) are randomized 1:1 to SOR 400 mg bid or matching PL orally on a continuous basis. Treatment cycles are repeated every 4 weeks until untreatable progression (defined as failure to achieve objective response after ≥2 TACE in the treated tumor nodule). TACE is performed on day 1 of cycles 1, 3, 7, 13, and every 6 cycles thereafter. All endpoints will be assessed on an ITT basis. The primary study endpoint is time to progression. Secondary endpoints are overall survival, time to untreatable progression, time to vascular invasion/extrahepatic spread, and safety. Estimated overall accrual is 300 subjects. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Bayer Bayer Bayer, Bristol-Myers Squibb Bayer 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 2010 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.