ECOG PS Status Research Articles

Hemoglobin, albumin, lymphocytes and platelets (HALP) score as a predictor of survival in patients with glioblastoma (GBM)

BackgroundWe aimed to investigate whether the HALP score was a predictor of survival in patients with Glioblastoma (GBM).MethodsA total of 84 Glioblastoma (GBM) patients followed in our clinic were included in the study. HALP scores were calculated using the preoperative hemoglobin, albumin, lymphocyte and platelet results of the patients. For the HALP score, a cut-off value was found by examining the area below the receiver operating characteristic (ROC) curve. Patients were divided into two groups as low and high according to this cut-off value. The relationships among the clinical, dermographic and laboratory parameters of the patients were examined using these two groups.ResultsMedian OS, PFS, HALP score, NLR, PLR were 15 months (1.0–78.0), 8 months (1.0–66.0), 37.39 ± 23.84 (min 6.00-max 132.31), 4.14, 145.07 respectively. A statistically significant correlation was found between HALP score and OS, PFS, NLR, PLR, ECOG-PS status using Spearman’s rho test (p = 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.026 respectively). For the HALP score, a cut-off value of = 37.39 (AUC = 0.698, 95% CI, p < 0.002) was found using ROC analysis. Median OS was 12 (6.99–17.01) months in the low HALP group and 21 (11.37–30.63) months in the high HALP group (p = 0.117). NLR and PLR were significantly lower in the HALP high group (p < 0.001, p < 0.001 respectively). The ratio of receiving treatment was significantly higher in the high HALP group (p < 0.05). In Multivariate analysis, significant results were found for treatment status and ECOG-PS status (p < 0.001, p = 0.038 respectively).ConclusionsThe HALP score measured at the beginning of treatment seems to have predictive importance in the prognosis of GBM patients. A HALP score of > 37.39 was associated with prolonged survival in high-grade brain tumors.

Second-Line Chemotherapy for Intrahepatic Cholangiocarcinomas: What Is the Real Gain?

The presence of actionable alterations in advanced biliary tract cancer patients opened new therapeutic possibilities for second-line treatments. However, for around 60% of the patients, chemotherapy remains the only therapeutic option. The aim of our study was to evaluate outcomes and prognostic parameters in patients with intrahepatic cholangiocarcinomas treated with second-line chemotherapy. A total of 255 consecutive metastatic intrahepatic cholangiocarcinoma (ICC) patients were retrospectively reviewed and clinicopathologic and survival data were collected. Fourty-four percent of ICC patients underwent second-line chemotherapy. In particular, younger ICC patients with better ECOG PS status, and with disease control after first-line chemotherapy were those who were treated with second-line treatments. Median progression-free survival in the patients treated with second-line chemotherapy was 3 months. Finally, the patients affected by intrahepatic cholangiocarcinoma with better ECOG PS, with prior surgical resection of the primary tumor, who responded to first-line chemotherapy, and had better progression-free survival with second-line chemotherapy, were associated with better outcomes in multivariate analysis. Not all patients seem to benefit from second-line chemotherapy. To improve therapeutic decisions, performance status and disease control with first-line chemotherapy should lead to the decision on the usefulness of second-line treatments in advanced ICC patients.

Efficacy of immune checkpoint inhibitors in microsatellite unstable/mismatch repair-deficient advanced pancreatic adenocarcinoma: An AGEO European Cohort.

4148 Background: Immune checkpoint inhibitors (ICI) have been approved for the use in solid tumors with MSI/dMMR. Nevertheless, the outcome of patients (pts) with MSI/dMMR pancreatic ductal adenocarcinoma (PDAC) seems poorer when compared to other malignancies. This multi-institutional analysis aimed to assess the efficacy and tolerability of ICIs in a large real-world cohort of pts with MSI/dMMR PDAC. Methods: Retrospective data were collected for pts with MSI/dMMR PDAC treated with ICIs from February 2016 to May 2022 in 16 different centers across Europe and Israel. Progression-free survival (PFS) and overall survival (OS) were calculated from the start of treatment, and objective response (OR) and disease control rate (DCR) were measured according to RECIST V1.1. Results: We identified 31 pts with metastatic MSI/dMMR PDAC. The mean age was 62.1 years (range: 37-82), 45.1% were female and ECOG PS status was predominantly 0 or 1 (83.9%). At the time of ICI treatment 1 pt had locally advanced and 30 had metastatic disease. MSH2/MSH6 deficiency (def) was found in 9 cases, MLH1/PMS2 def in 7, MSH 6 def in 4, MSH 2 def in 3, PMS2 def in 3 and MLH1/MSH6/PMS2 def and, a CpG highland methylator phenotype in 1 pt. MMR status was not available in 4 pts. Germline mutation testing was performed in 20/31 pts (64.5%) and Lynch syndrome was diagnosed in 8 pts (45%). Nineteen pts received pembrolizumab, 8 received nivolumab, 1 received lodapolimab and 3 received ipilimumab/nivolumab (ipi/nivo). The mean number of prior lines of chemotherapy was 1.5 (range 0-4). Among the 31 pts in this analysis, 15 (48,4%) had an OR (3: complete response and 12 partial response) and 6 (19,3%) had stable disease, resulting in a DCR of 67.7%. Ten pts had disease progression (PD) (32.3%). Median PFS was 26.7 months and median OS was not reached with median follow-up (FU) of 18 months. Median duration of response was not reached (95%CI:24.1-NR). Analysis of all responders, with a follow up of 12 months or more (n:14), showed that 100% of them maintained their response. In addition 71% of the pts of this cohort are still alive with a median time of follow up since the diagnosis of metastatic disease of 39.9 months. After ICIs discontinuation, 6 pts received chemotherapy. One pt who had PD after 15 months of pembrolizumab switched to ipi/nivo and achieved a CR. Immunotherapy was generally well tolerated; No Grade 3-5 adverse events (AEs) were reported and no therapy discontinuation due an adverse event was observed. Conclusions: This retrospective analysis suggests that ICIs are effective and well tolerated in pts with MSI/dMMR advanced PDAC. Hence, our work supports the use of PD-1 inhibition in this group of pts with high unmet medical need.

Abstract PD11-05: PD11-05 Gut microbiome signatures correlate with overall survival among patients receiving eribulin with or without pembrolizumab for hormone receptor-positive metastatic breast cancer

Abstract Background: The gut microbiome modulates response and resistance to immune checkpoint inhibitors (ICI) across different cancer types. The objective of this study was to explore the association between fecal microbiome profiles and clinical outcomes in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC) treated with eribulin (E) + pembrolizumab (P) or E alone as part of a randomized phase II study (NCT03051659). Patients and Methods: Metagenomic shotgun sequencing was performed on fecal samples collected prior to randomization from a subset of 26 participating patients (E+P, n = 15; E, n = 11) collected prior to randomization. Sequencing data were processed with MetaPhlAn3 to obtain diversity scores and taxonomic composition profiles. Associations between microbiome diversity, taxonomic composition, and clinical outcomes including survival metrics were assessed using Kaplan-Meier estimation methods and Cox proportional hazard models. Results: In this subset, median follow-up was 21.6 months and median overall survival (OS) was 17.9 months. OS was not statistically significant between two treatment arms as observed in the overall cohort. Metagenomic microbiome analysis revealed higher alpha diversity by inverse Simpson Index values associated with longer survival among all patients (p = 0.004), and in patients in the E + P arm (p = 0.006) but not in the E arm (p = 0.2). At the taxonomic level, longer OS among all patients was associated with a baseline lower relative abundance of Blautia wexlerae (≤0.2%vs &amp;gt;0.2%) (22.1 vs 16.6 months; p = 0.01) and a higher relative abundance of Odoribacter splanchnicus, a common short-chain fatty acid producing gut bacterium (&amp;gt;0.35% vs ≤0.35%) (22.3 vs 11.3 months; p &amp;lt; 0.0001). These associations remained significant after controlling for age, ECOG-PS status, and use or not of prior lines of chemotherapy in the metastatic setting. Conclusions: These results suggest high diversity and composition of the gut microbiome are associated with prolonged OS in HR+ MBC pts receiving eribulin with pembrolizumab. Additional and larger clinical studies are needed to validate these findings and preclinical models are needed to interrogate the mechanisms by which gut microbiome diversity and composition may impact therapeutic response and clinical outcomes in this patient population. Citation Format: Romualdo Barroso-Sousa, Tianyu Li, Ashish V. Damania, Molly K. DiLullo, Tanya Keenan, Gerburg M. Wulf, Laura M. Spring, Elizabeth A. Mittendorf, Jennifer A. Ligibel, Nadim J. Ajami, Jennifer Wargo, Nabihah Tayob, Sara Tolaney. PD11-05 Gut microbiome signatures correlate with overall survival among patients receiving eribulin with or without pembrolizumab for hormone receptor-positive metastatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD11-05.

Safety and efficacy of encorafenib, binimetinib, plus cetuximab for BRAF V600E-mutant metastatic colorectal cancer: Results of a prospective study as an expanded access program.

199 Background: The encorafenib, binimetinib, and cetuximab (triplet) regimen showed survival benefit and a higher response rate over standard chemotherapy among pretreated patients (pts) with BRAF V600E-mutant metastatic colorectal cancer (mCRC) in the phase III BEACON trial. Herein, we report the safety and efficacy of the triplet regimen in a prospective study (JapicCTI-205146) as a Japanese expanded access program (EAP). Methods: The key eligibility criteria were age ≥18 years and a diagnosis of BRAF V600E-mutant mCRC with progression observed after one or two prior systemic chemotherapy. Encorafenib (300 mg QD), binimetinib (45 mg BID), and weekly cetuximab (400 mg/m2, followed by 250 mg/m2) were administered. Patients who had received at least one dose of any study drug were included in this analysis. Adverse events were evaluated using CTCAE v4.0. The objective response rate (ORR) was evaluated using RECIST Guideline Version 1.1. Results: A total of 86 pts were enrolled from 10 Japanese institutions from February to December 2020. Safety and efficacy were evaluated in 81 pts. The median age was 60 years. Fifty-four pts (67%) had ECOG PS 0 and 50 pts (62%) received one prior chemotherapy. Treatment-related serious adverse events and grade 3 or higher treatment-related adverse events were observed in 14 (17%) and 24 (30%) pts, respectively. Treatment-related death occurred in one pts. Among the 76 pts with target lesions, 21 pts were responders, and the confirmed ORR was 27.6%. Stable disease was observed in 42 pts, resulting in a disease control rate of 82.9%. The ORR was consistent regardless of ECOG PS status, the number of prior chemotherapy lines, and the number of metastatic organs. Conclusions: The safety and efficacy of the triplet regimen in the Japanese EAP were comparable to those in the BEACON trial. These results support the triplet regimen as a new standard-of-care treatment option in the second- or third-line treatment of pts with BRAF V600E-mutant mCRC in the Japanese population, as there was a promising response without any new safety signals. Clinical trial information: JapicCTI-205146.

Immune checkpoint inhibitors and hospitalization at home in France

The administration of immune checkpoints inhibitors (ICIs) within hospitalization at home (HaH) organizations is an interesting alternative to conventional care. Three surveys were carried out to describe the different organizational models of French HaHs and criteria used by physicians in patient selection. Three surveys were conducted between April 1 and August 31, 2020. The first one was addressed to all French HaHs, and the two others to public HaHs and oncologists treating patients with solid cancer in the Auvergne-Rhone-Alpes region. Overall, 54 French HaHs and 23 oncologists participated to the study. The health professionals involved in the patients' care were very heterogeneous, although in 92% of cases, the treatment prescription was made by the oncologist. HaH physicians were more involved in clinical assessment the day before treatment (19% vs. 0%), treatment validation (56% vs. 15%), and treatment prescription (19% vs. 0%), while nurses were better equipped (emergency kit available in 81% versus 50% of cases) when HaHs did carry out ICIs compared to when they did not. Most oncologists agreed that age, neuropsychiatric disorders, home environment, as well as treatment duration and good tolerance should be considered in patient selection. ECOG PS status and treatment response were less consensually considered. These results highlight the variability in French HaH organizations and patient selection criteria for employing ICIs at home. This study resulted in recommendations for administrating ICIs in HaH settings, which will likely be instrumental in further promoting this activity across France.

High fibrinogen-albumin ratio index predicts poor prognosis for lung adenocarcinoma patients undergoing epidermal growth factor receptor-tyrosine kinase inhibitor treatments.

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) have become the preferred therapy as first-line treatment of non-small cell lung cancer patients harboring sensitizing EGFR mutations. However, the prognostic indicators are limited. The present study aimed to assess the prognostic value of immune-inflammation factors, fibrinogen-albumin ratio index (FARI), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) in EGFR-Mutant lung adenocarcinoma patients receiving first-generation EGFR-TKIs treatment.194 patients were included in this retrospective analysis. FARI was calculated as fibrinogen / albumin. Receiver operating characteristic curve was used to evaluate the optimal cut-off value for FARI, NLR, and PLR to progression free survival (PFS). Univariate and multivariate survival analysis were performed to identify factors correlated with PFS and overall survival (OS).Applying cut-offs of ≥0.08 (FARI), ≥3.28 (NLR), and ≥273.85 (PLR), higher FARI or NLR was associated with worse Eastern Cooperative Oncology Group performance status (ECOG PS) (P = .018, .002, respectively), and there were more males in high NLR group (P = .043). In univariate analysis, ECOG PS status, NLR, PLR, and FARI were significantly associated with PFS (P = .017, .004, <.001, .001, respectively) as well as OS (P < .001, = .001, .002, .023, respectively). In multivariate analysis, PLR (hazard ratios [HR] 1.692; 95% CI 1.054–2.715; P = .029) and FARI (HR 1.496; 95% CI 1.031–2.172; P = .034) were independent prognostic factors for PFS. While only ECOG PS status (HR 2.052; 95% CI 1.272–3.310; P = .003) was independently correlated with OS.FARI is independently associated with PFS in EGFR-Mutant lung adenocarcinoma patients receiving first-line EGFR-TKIs treatment.

Real-World Effectiveness and Safety of Nivolumab in NSCLC pts in Japan: A Multicenter-Retrospective Observational Study

Abstract Background In December 2015, nivolumab was approved as treatment for previously treated NSCLC irrespective of PD-L1 expression or histology in Japan. There are few reports that include real-world data on large cohorts of patients from Japan. Method Data from patients who initiated nivolumab treatment from April 1, 2016 to December 31, 2016 were collected at 23 regional medical institutions across Japan. Here we report a retrospective data analysis accessing effectiveness and safety of nivolumab in 901 Japanese NSCLC pts from a multicenter, observational study; CA209-9CR (NCT03273790). Result Among 901 pts, median age of the pts treated with nivolumab was 67 ys old and proportion of 75 ys or over was 19.8%. Pts with ECOG PS 0 or 1 account for 75.8%, and pts with SQ and adeno histology were 24.5% and 67.7%, respectively. Pts with EGFR mutation account for 12.9%. Median numbers of nivolumab dose was five and nivolumab was most frequently used at 2nd line (46.8%) and followed by at 3rd line (26.5%). Rate of 1 yr overall survival (OS) was 54.3% and, median PFS was 2.1 months and overall ORR was 20.6%. There was no significant difference in effectiveness among histology. Although there was no difference in effectiveness of nivolumab by age, ECOG PS status significantly influence effectiveness of nivolumab. Analysis is ongoing to access various factors that may be associated with the effectiveness of nivolumab. Overall irAE incidence for all grade and grade 3-4 will be reported as well as categorized irAE. Further analysis is planned for safety management of irAEs and prognosis. Conclusion The effectiveness and safety of nivolumab observed in real-world data from NSCLC patients in Japan was comparable to results observed in clinical trials. ECOG PS status was identified as a factor influencing effectiveness of nivolumab.

Development and evaluation of a proxy for baseline ECOG PS in advanced non-small cell lung cancer (aNSCLC), bladder cancer (aBCa), and melanoma (aMM): An electronic health records (EHR) study.

e18194 Background: Performance status measured by ECOG PS (ECOG) predicts therapy choice, and overall survival (OS), but often not reported in routine care. EHR data include rich clinical information which Methods: In this retrospective analysis using Flatiron Health EHR-derived database we selected patients diagnosed from 2011-2018 with aNSCLC, aBCa, and aMM and ECOG reported between diagnosis and 1) therapy start, or 2) within 90 days. We used multivariable logistic regressions in a 75% development sample to model associations between selected sociodemographic, clinical and laboratory measures and poor ECOG (2+ vs 0-1) for each cancer. Predictive accuracy was assessed in 25% validation datasets. Kaplan-Meier analysis tested the associations between observed and predicted poor ECOG with OS. Results: The non-missing ECOG samples were 20,697 aNSCLC, 2627 aBCa, and 2558 aMM (out of 50,876, 6955, and 7917 respectively). The proportion of patients with ECOG 2+ ranged from 28.5% for aNSCLC to 15% for aMM. Higher number of comorbid conditions, older age, lowest BMI, higher number of metastases, abnormal albumin and hemoglobin and public insurance were associated with poor ECOG status. Predictive accuracy for poor baseline ECOG was 71.8% for NSLCL, 73.8% for aBca, and 85.4% for aMM). There was a consistent association between OS and observed and predicted baseline ECOG (Table 1). Conclusions: In a large cohort of cancer patients, routinely collected EHR data were used to predict baseline ECOG PS status. Complete ECOG status results may enhance evaluation of cancer treatment patterns and outcomes in EHR data. [Table: see text]

Impact of new systemic therapies on overall survival (OS) of patients (pts) with metastatic castration resistant prostate cancer (mCRPC) in a hospital-based registry.

203 Background: From 2004 to 2009, mCRPC treatment options were limited to docetaxel (D), mitoxantrone, first generation anti-androgens (AA), estrogens, steroids, and ketoconazole, with only D showing OS benefit. Since 2010, five new therapies prolonged OS and were approved for mCRPC: sipuleucel-T, cabazitaxel, abiraterone acetate, enzalutamide, and radium 223. We sought to assess the aggregate impact of new therapies on OS. Methods: We used the DFCI CRIS database to identify cohorts of pts who developed mCRPC between 2004-2007 (cohort A) and 2010-2013 (cohort B). Therapies for mCRPC in each cohort were annotated. Given the median follow-up (FU) was 10.6 years (yrs) in cohort A and 4.6 yrs in cohort B, we evaluated OS, defined as time from mCRPC per PCWG3 criteria to death from all causes or last follow-up visit within 5 yrs (truncated OS). Kaplan-Meier method estimated the time to events distribution with median (95% CI). Cox proportional hazards model evaluated effects of treatment groups on disease outcomes with estimates of hazard ratio (95% CI). Results: Of the 583 pts identified, 317 (54%) were in cohort A and 266 (46%) in cohort B. Pts in cohort B had a significantly longer median OS (p&lt;0.001), a 5-yr OS of 26% vs. 10%, and a 31% reduced risk of death compared to cohort A (HR=0.69; 95% CI, 0.57-0.83) (see Table). On multivariable analysis, adjusting for prior local Rx, ECOG PS, and the number of agents received, longer OS is confirmed associated with cohort B vs. A and also with ECOG PS status 0 vs. 1, number of agents received 5-12 vs. ≤3. Conclusions: Using the DFCI prostate cancer database, therapies approved for mCRPC since 2010 showed a modest impact on OS, with a median improvement of 6 months. There was a more substantial effect on long term survivors with 2.6 fold increase of 5-yr OS. [Table: see text]

The Effects of Palliative Chemotherapy in Metastatic Colorectal Cancer Patients With an ECOG Performance Status of 3 and 4

BackgroundAlthough chemotherapy is standard for patients with mCRC and ECOG PS of 0/1, the real benefit for patients with ECOG PS > 2 remains uncertain, because they are generally excluded from clinical trials. Our objectives were to compare the survival and safety of ECOG PS 3/4 patients who were administered chemotherapy with those who received BSC only. Patients and MethodsWe retrospectively analyzed all consecutive mCRC patients who started first-line chemotherapy at our institution in a 4-year period. A multivariable Cox regression model was used to adjust for prognostic factors and logistic regression, to identify predictive factors of Grade 3/4 toxicity. ResultsFrom June 2008 to June 2012, 240 consecutive patients were included: 100 (41.7%) had an ECOG PS of 0/1, 75 (31.3%) ECOG PS of 2, and 65 (27%) ECOG PS of 3/4. Median survival for patients treated with chemotherapy was 18.4 months for patients with ECOG PS of 0/1, 10.8 months for those with ECOG PS of 2, and 6.8 months for patients with ECOG PS of 3/4. Among those with ECOG PS of 3/4, chemotherapy use led to a nonsignificant survival gain (median, 6.8 vs. 2.3 months for BSC; P = .13). Factors significantly associated with worse survival in an adjusted analysis were right-sided tumors (hazard ratio [HR], 2.97; P = .005) and ECOG PS status (ECOG PS 2 vs. 0/1; HR, 1.67; P = .025, and ECOG PS 3/4 vs. 0/1; HR, 2.67; P < .0001). The rate of Grade ≥ 3 toxicities during the first cycle did not differ significantly across ECOG groups; likely because 40% of ECOG PS 3/4 patients received upfront dose-reduced therapy. The rates of treatment-related hospitalization were similar across all ECOG groups. All deaths were disease-associated. ConclusionOur retrospective study suggests that chemotherapy might benefit selected mCRC patients with poor PS. With up-front dose reduction and close monitoring for toxicity, the risk of serious adverse events is minimized.

MDR1 single nucleotide polymorphism C3435T in Turkish patients with non-small-cell lung cancer

We assessed whether single nucleotide polymorphisms (SNPs) in MDR1 gene C3435T predicted the outcome of platinum-based chemotherapies and survival in our non small cell lung cancer (NSCLC) patients. A total of 79 non-small cell lung cancer patients were enrolled to study. We determined the MDR1 C3435T single nucleotide gene polymorphisms. Median age was 60years: 91.7% male, 8.9% female. We found that CC, CT, TT genotype and T, C allele frequencies in lung cancer patients as 24.1%, 62%, 13.9% and 44.3%, 55.7%, respectively. Patients with CT genotype had a higher response rate (11.4%) than the other genotypes. However, this difference is not statistically significant (p=0.743). Cox regression analysis for overall survival showed that ECOG PS status 0 (HR PS 1 vs. 0, 5.68 p=0.002; HR of PS 2 vs. 0 is 21.579, p=0.001; HR of PS 3 vs. 0 is 35.35, p=0.001), stage ≤II (HR of stage III vs. I+II is 17.77; p=0.016, HR of stage IV vs. I+II is 26.97, p=0.006), and albumin level ≥3g/dl (HR of albumin <3g/dl vs. ≥3g/dl is 2.46, p=0.044) were the most important prognostic factors (also, time to progression was related to these factors). There was no significant association between the genotypes and clinicopathologic parameters; however, good performance status, early stage and ≥3g/dl albumin level were found to be the most important prognostic factors for overall survival and progression-free survival.

P-0062 Second-Line Chemotherapy for Patients with Metastatic Gastric Cancer: a Retrospective Analysis

IntroductionGastric cancer is the fourth most common cancer and the second most common cause of cancer deaths in the world. Many patients (pts) present with locally advanced unresectable or metastatic disease when first diagnosed. Treatment with second-line chemotherapy remains controversial. The aim of this study is to evaluate the time to progression (TTP) after second-line chemotherapy of pts with metastatic gastric cancer. MethodsThis retrospective analysis was based on data obtained from 84 pts treated with a first-line chemotherapy regimen for metastatic gastric cancer in our oncology department (January 2005 to May 2010). The primary endpoint of this study was TTP measured from the beginning of second-line treatment to the date of progression, accessed by imaging and/or clinical criteria. The secondary endpoint was survival after second-line chemotherapy, measured from the beginning of second-line chemotherapy to the date of death or last follow-up visit. ResultsFrom the 84 pts who completed first-line chemotherapy, 38 (45%) were able to receive second-line chemotherapy; all others had died from disease progression or had a poor performance status. Of the 38 pts, 26 (68%) were male and 12 (32%) female, with a median age of 64 years (range 46-80 years), 24% of the pts had histology compatible with mucinous adenocarcinoma (ADC). 27 pts had Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2, and 11pts had unknown ECOG PS status. Chemotherapy regimens used for second-line treatment were: Taxanes 19 pts (50%), combination of oxaliplatin/5-FU (FOLFOX) 8 pts (21%), combination of irinotecan/5-FU (FOLFIRI) 7pts (18%), Irinotecan 3 pts (8%), and Mitomycin in 1 pts (3%). There were no treatment-related deaths. One patient (3%) had a complete response, 4 pts (11%) had partial response, and 14 pts (36%) had stable disease. The median TTP and survival after second-line chemotherapy were 2.73 months and 6 months, respectively. ConclusionDespite the patients with good performance status after first-line chemotherapy failure, the TTP and survival after second-line chemotherapy is relative short but consistent with the literature data.

A single-arm, open-label, U.S. expanded access study of vemurafenib in patients with metastatic melanoma.

8567 Background: Vemurafenib (vem) has been FDA approved for the treatment of unresectable or metastatic BRAFV600E mutated melanoma since August 2011 based on results of a randomized phase III study (treatment-naive) and a single arm phase II study (previously treated). We report results of an expanded access study that allowed appropriate patients (pts) to receive vem until the drug was approved. Methods: Eligible pts had metastatic melanoma with a BRAFV600E mutation as detected by the cobas 4800 BRAFV600 Mutation Test. Enrolled pts received oral vem 960 mg b.i.d. Adverse events (AEs) were evaluated for vem-related toxicities; tumor responses were assessed using RECIST 1.1. Results: 29 US sites screened 745 pts and enrolled 374 from December 2010 until October 2011. The following results are based on a median follow up time and treatment duration of 2 months. At baseline, mean age of pts was 54 y with 22% of pts ≥65 y; 75% had stage M1c disease; 29% had received radiotherapy for brain metastases. 19% of pts were ECOG PS 2 or 3; 71% of pts had prior systemic therapy for metastatic melanoma (21% 1 regimen; 50% ≥2 regimens). 50 pts had prior adjuvant treatment. At data cut-off, 243 pts had sufficient follow-up time for tumor assessment. In this group, the unconfirmed overall response rate was 52% (95% CI, 46 to 59). The median time to response was 1.8 months. Based on 240 pts with available ECOG PS status at time of analysis, response rate was 53% for pts with ECOG PS 0 or 1 (n=209), and 45% for pts with ECOG PS 2 or 3 (n=31). 370 pts were evaluable for safety analysis. The most common vem-related AEs were rash (36%), arthralgia (33%) and fatigue (21%) with the majority (~90%) of grade 1 or 2. 25 vem-related serious AEs were reported in 5.4% of pts with a slightly higher rate of pts with ECOG PS 2 or 3 (8.7%) compared to ECOG PS 0 or 1 (4.7%). 18% of pts missed at least one dose and 11% of pts required dose reduction of at least one level due to AEs. Conclusions: This expanded access study, with its limited follow-up time, confirms the established rapid and high tumor response rate with vem. No new safety signals were detected. Compared to the overall population, pts with an ECOG PS 2 or 3 demonstrated a similar benefit.

Patterns of Care for Patients with Chronic Lymphocytic Leukemia (CLL): The Connect® CLL Disease Registry

Abstract 2864 Introduction: Clinical trials have illuminated a number of unique treatment strategies for patients with CLL. The impact of these strategies on routine practice remains unknown as trial participants may not reflect the same population encountered outside of a clinical trial setting. Many questions remain regarding the sequencing of therapies based on age and performance status. By characterizing current patterns of care; patients, treating physicians, and regulatory agencies will be able to understand the current landscape of CLL treatment. The Connect ® CLL registry was designed to report the natural history and real world management of patients receiving therapy for CLL. In this first report, we characterize the therapeutic approaches used for the treatment of patients with CLL of different age groups (i.e. Methods: Connect ® CLL is a prospective, longitudinal, observational, multi-center registry conducted in community and academic research centers in the United States. At present, 237 sites are actively participating with a projected study enrollment of 1500 patients. Eligible patients are to be enrolled within 2 months of being initiated on any line of therapy; whether initial therapy or salvage therapy. Each patient will be followed for up to 60 months. Clinical data, physician choices, patient-reported health-related quality of life, response and survival are to be collected approximately every 3 months during participation. Results: A total of 607 patients have been enrolled (4% from academic sites) with a median age of 70 years. 198 were The use of FCR for first-line treatment decreased significantly with increasing age group, (45%, 32%, 20%, for age group 1, 2, 3 respectively, p=0.04, spearman correlation) while use of F +/− R remained level across the age groups (14%, 15%, 15%, respectively). Compared to age group 1, first-line therapy with B +/− R in age groups 2 and 3 (15%, 22%, 21%, respectively) was higher but did not achieve statistical significance. B +/− R represented the most common treatment for all age groups (37%, 26%, 29%, respectively) as second line therapy but did not vary by age (P=0.35). The use of chlorambucil was infrequent in all age groups, but was more common in age group 3 patients compared to the others (P=0.01), in both first-line (2%, 4%, 12%, respectively) and subsequent lines of therapy (0%, 1%, 8%, respectively). Treatment assignments did not vary by ECOG PS score for patients in age group 1. First-line therapy for patients with an ECOG PS score of 0 in age groups 2 and 3 consisted of FCR (32% and 15%, respectively), F +/− R (19% and 15%, respectively), B +/− R (16% and 15%, respectively), and alkylating agents (3% and 23%, respectively). Patients in age groups 2 and 3 with ECOG PS score ≥ 1 received B +/− R regimen (33% and 22%, respectively), FCR (23% and 21%, respectively), F +/− R (14% and 10%, respectively) and alkylating agents (7% and 9%, respectively) as first-line therapy. Further description and clarification on the various treatment regimens based on the three age groups and by ECOG PS score will be presented at the meeting. Conclusion: The Connect ® CLL Registry is the largest prospective, multicenter registry in the United States evaluating management for patients with CLL. With the currently available data, we characterize the extent to which age and performance status are associated with treatment selection in both first-line and subsequent lines of therapy in routine practice. As enrollment increases and additional follow-up is completed, the data will provide more extensive and real world overview of the current treatment strategies used in CLL patients. Disclosures: Sharman: Celgene - consulting: Consultancy; Pharmacyclics: Honoraria; Calistoga: Honoraria; Portola pharmaceuticals: Consultancy. Flowers: Consultancy: Celgene, Prescription Solutions, Spectrum (future), Seattle Genetics, Millennium (future), Genentech (unpaid): Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding. Weiss: Celgene: Consultancy. Grinblatt: Celgene: Honoraria, Speakers Bureau. Kay: Genenetech, Celgene, Hospira,: Research Funding. Kipps: Igenica: Equity Ownership, Membership on an entity9s Board of Directors or advisory committees; Celgene: Consultancy, Research Funding; Abbot Industries: Research Funding; Pharmacyclics: Membership on an entity9s Board of Directors or advisory committees; Genentech: Research Funding; GSK: Research Funding; Gilead Sciences: Research Funding; Amgen: Research Funding. Lamanna: Celgene Corporation: Advisory board. Pashos: United BioSource Corporation: Research Funding. Flinn: Celgene: Research Funding. Kozloff: Celgene: Consultancy. Lerner: Celgene Connect: Membership on an entity9s Board of Directors or advisory committees. Swern: Celgene: Employment. Sullivan: Celgene: Employment. Street: Celgene: Employment. Keating: Celgene Connect: Membership on an entity9s Board of Directors or advisory committees.

Phase II trial of combined temozolomide and pegylated liposomal doxorubicin in the treatment of patients with glioblastoma multiforme following concurrent radiotherapy and chemotherapy.

2072 Background: Concurrent and post-radiotherapy temozolomide (TMZ) significantly improves survival in patients (pts) with newly diagnosed Glioblastoma Multiforme (GBM). Pegylated liposomal doxorubicin (D) has been evaluated in preclinical models and noted to penetrate the blood brain barrier. A phase I study confirmed that the combination of TMZ and D can be used safely at full doses. Phase II data supports efficacy of this combination in recurrent GBM. Methods: Eligible pts had histologically confirmed GBM, completed concurrent postoperative chemoradiotherapy (CRT) to 60Gy with TMZ (75 mg/m2 orally daily) according to the EORTC protocol, were considered suitable for further post CRT chemotherapy and had an ECOG PS 0-2. Post-CRT TMZ (initially 150 mg/m2 then increased to 200 mg/m2 orally, days 1-5) and D (40 mg/m2 intravenously day 1) were administered every 4 weeks for a maximum of 6 cycles. The primary endpoint was an improvement in 6 month progression-free survival (6-m PFS) measured from the date of registration on trial (after concurrent chemotherapy and irradiation), based on a Simon two stage approach with 40 pts as the planned total to be enrolled. Results: 40 eligible pts were enrolled: median age 53 years (range 24-76); ECOG PS status 0 (53%), 1 (40%), 2 (7%) and 73% were male. Six month PFS was 56% (95%CI 41-72%). PFS was comparable with pts in the EORTC study (personal communication R Stupp) matching these definitions. Median time to progression and overall survival (OS) were 6.1 months (95%CI 5.6-8.0 months) and 13.4 months (95%CI 10.2-17.3 months) respectively. Of 34 evaluable pts, one patient had a complete response (CR) (3%) and 28 had stable disease (SD) (70%). Treatment was well tolerated. There was one pt (3%) with grade 4 neutropenia. Three pts (8%) had grade 3 neutropenia and one grade 3 thrombocyotopenia was observed. Grade 3/4 non-hematologic toxicity included: palmar-plantar toxicity in 2 pts (5%) and a reaction to D in 1 patient (3%). Conclusions: The combination of TMZ and D is well tolerated, but based on the observed 6 PFS and OS, does not appear to add significant clinical benefit in the treatment of newly diagnosed GBM. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough Schering-Plough

Bevacizumab (BV) plus chemotherapy (CT) as first-line treatment of patients with metastatic colorectal cancer (mCRC): First results from a large community-based observational cohort study in Germany

e15057 Background: BV prolongs overall survival (OS) and progression-free survival (PFS) when added to standard CT for patients (pts) with mCRC. After approval of BV in Germany in 01/05, this observational cohort study was initiated in pts receiving BV with various first-line CT regimens to evaluate safety events and effectiveness. Methods: To facilitate and evaluate enrollment of a typical mCRC population, eligibility criteria were minimized. Choice of the CT regimen was at physician´s discretion, but influenced by the current registration status. Predefined endpoints were treatment characteristics, response rate (RR), PFS, OS, and adverse events assessed as potentially related to the treatment (AERT) or as severe (SAE). Pts are followed for up to 4 years, and clinical data were updated every cycle (2–4 weeks). Results: 1,300 pts were enrolled at 261 sites from 01/05 through 06/08; abstract data cutoff date was 11/24/08. Median age: 64 (range 19–100) years, &gt; 70 years.: 25%; male 63%; ECOG PS status 0–1/2/&gt;2 88%/11%/1%. CT choice was fluoropyrimidine (FU)/BV alone (any 5-FU or capecitabine) 12%; FU/BV/oxaliplatin 18%; FU/BV/irinotecan 69%; other 1%. Median treatment duration with BV was 7.4 (range 0–28) months; duration &gt; 10 months 21%. 60-day mortality was 4.0%. In total, 183 AERT were reported in 10% of pts., most commonly diarrhea (34 AERT), nausea (26) and hypertension (18). Reported SAE were deep venous TE in 0.8% of pts, bleeding 1.2%, pulmonary embolism 0.5%, arterial TE 0.4%. Best investigator- assessed RR was 59% (CR 10%, PR 49%; all pts) with 64% for FU/BV/oxaliplatin, 59% for FU/BV/irinotecan and 53% for FU/BV alone. Conclusions: The safety profile of BV in this population of mCRC pts with different CT regimens appears consistent with that observed in the other reports like BRiTE or first BEATrial. RR in this preliminary dataset are higher than that reported in the randomized controlled trials, but likely biased by the methodology of evaluation. However, activity with FU/BV alone was surprisingly high. Updated efficacy data including PFS will be presented. [Table: see text]