No abstract

Genentech and Novartis Pharmaceuticals.

Bevacizumab beyond first progression represents an option for patients with mCRC treated with bevacizumab plus standard first-line chemotherapy, independent of KRAS status.

No abstract

CRA3503 Background: BEV in combination with fluoropyrimidine-based CT is standard treatment for mCRC in the first-line (1L) and BEV-naïve second-line (2L) settings. This is the first randomized study evaluating the benefit of continuing BEV in combination with standard CT as 2L treatment for patients with mCRC who progressed after receiving a standard BEV-containing regimen in the 1L setting. Methods: Patients with unresectable, histologically confirmed mCRC who progressed within 3 months after discontinuation of 1L BEV + CT were randomised to 2L fluoropyrimidine-based CT ± BEV (2.5 mg/kg/wk equivalent). Choice of oxaliplatin- or irinotecan-based 2L CT was dependent on the regimen used in 1L (crossover) and included as a stratification variable. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), response rate and safety. Results: 820 patients were randomized from February 2006 to June 2010 (409 to BEV + CT and 411 to CT alone). Baseline patient and disease characteristics were well balanced between arms. The study met its primary endpoint; median OS was 11.2 months for BEV + CT and 9.8 months for CT (HR=0.81; 95% CI 0.69–0.94; unstratified log-rank test, p=0.0062). Median PFS was 5.7 months for BEV + CT and 4.1 months for CT (HR=0.68; 95% CI 0.59–0.78; unstratified log-rank test, p<0.0001). The response rate was 5.4% for BEV + CT and 3.9% for CT (unstratified Chi-Square Test, p=0.3113). The adverse event profile was consistent with previously reported data for BEV + CT. Compared with historical data from BEV treatment in 1L or 2L mCRC, BEV-related adverse events were not increased when continuing BEV beyond progression. Conclusions: This is the first randomized study to prospectively investigate the impact of continuing BEV treatment in 2L mCRC for patients who progressed after receiving a BEV-containing regimen in 1L. Our findings demonstrate that BEV + CT (crossed over from 1L regimen) continued beyond progression significantly prolongs OS and PFS in 2L mCRC. Additional analysis (including biomarker evaluation) is ongoing.

Background The efficacy of bevacizumab (BEV) in elderly patients with glioblastoma remains unclear. We evaluated the effect of BEV on survival in this patient population using the Survival, Epidemiology, and End Results (SEER)-Medicare database. Methods This retrospective, cohort study analyzed SEER-Medicare data for patients (aged ≥66 years) diagnosed with glioblastoma from 2006 to 2011. Two cohorts were constructed: one comprised patients who had received BEV (BEV cohort); the other comprised patients who had received any anticancer treatment other than BEV (NBEV cohort). The primary analysis used a multivariate Cox proportional hazards model to compare overall survival in the BEV and NBEV cohorts with initiation of BEV as a time-dependent variable, adjusting for potential confounders (age, gender, Charlson comorbidity index, region, race, radiotherapy after initial surgery, and diagnosis of coronary artery disease). Sensitivity analyses were conducted using landmark survival, propensity score modeling, and the impact of poor Karnofsky Performance Status. Results We identified 2603 patients (BEV, n = 597; NBEV, n = 2006). In the BEV cohort, most patients were Caucasian males and were younger with fewer comorbidities and more initial resections. In the primary analysis, the BEV cohort showed a lower risk of death compared with the NBEV cohort (hazard ratio, 0.80; 95% confidence interval, 0.72–0.89; P < .01). The survival benefit of BEV appeared independent of the number of temozolomide cycles or frontline treatment with radiotherapy and temozolomide. Conclusion BEV exposure was associated with a lower risk of death, providing evidence that there might be a potential benefit of BEV in elderly patients with glioblastoma.

CRA3503 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.

PURPOSE External control (EC) arms derived from electronic health records (EHRs) can provide appropriate comparison groups when randomized control arms are not feasible, but have not been explored for metastatic colorectal cancer (mCRC) trials. We constructed EC arms from two patient-level EHR-derived databases and evaluated them against the control arm from a phase III, randomized controlled mCRC trial. METHODS IMblaze370 evaluated atezolizumab with or without cobimetinib versus regorafenib in patients with mCRC. EC arms were constructed from the Flatiron Health (FH) EHR-derived de-identified database and the combined FH/Foundation Medicine Clinico-Genomic Database (CGDB). IMblaze370 eligibility criteria were applied to the EC cohorts. Propensity scores and standardized mortality ratio weighting were used to balance baseline characteristics between the IMblaze370 and EC arms; balance was assessed using standardized mean differences. Kaplan-Meier method estimated median overall survival (OS). Cox proportional hazards models estimated hazard ratios with bootstrapped 95% CIs to compare differences in OS between study arms. RESULTS The FH EC included 184 patients; the CGDB EC included 108 patients. Most characteristics were well-balanced (standardized mean difference < 0.1) between each EC arm and the IMblaze370 population. Median OS was similar between the IMblaze370 control arm (8.5 months [95% CI, 6.41 to 10.71]) and both EC arms: FH (8.5 months [6.93 to 9.92]) and CGDB (8.8 months [7.85 to 9.92]). OS comparisons between the IMblaze370 experimental arm and the FH EC (hazard ratio, 0.85 [0.64 to 1.14]) and CGDB EC (0.86 [0.65 to 1.18]) yielded similar results as the comparison with the IMblaze370 control arm (1.01 [0.75 to 1.37]). CONCLUSION EC arms constructed from the FH database and the CGDB closely replicated the control arm from IMblaze370. EHR-derived EC arms can provide meaningful comparators in mCRC trials when recruiting a randomized control arm is not feasible.