PLS-5 - Results of ML18147: A Phase III Study of Bevacizumab in Second-Line MCRC for Patients Pretreated with Bevacizumab in First Line

Abstract

ABSTRACT Background BEV in combination with fluoropyrimidine-based CT is a standard treatment of mCRC in the first-line (1L) and BEV-naive second-line (2L) settings. This is the first randomized study evaluating the benefit of continuing BEV in combination with standard CT as 2L treatment of 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 randomized to 2L fluoropyrimidine-based CT ± BEV (2.5 mg/kg/week 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 end point was overall survival (OS); secondary end points included progression-free survival (PFS), response rate and safety. Results Eight hundred and twenty patients were randomized from February 2006 to June 2010. Baseline patient and disease characteristics were well balanced between the arms. The study met its primary end point of OS. Patients who received BEV + CT as 1L for their mCRC and then continued on BEV with a different CT after their cancer progressed lived significantly longer than patients who received only CT in the 2L mCRC. The adverse event profile was consistent with previously reported data for BEV + CT. Compared with the 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 in 2L mCRC. Additional analysis (including biomarker evaluation) is ongoing. Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that a phase III study (ML 18147) in metastatic colorectal cancer met its primary end point of overall survival. People who received Avastin® (bevacizumab) plus standard chemotherapy as initial treatment (so-called ‘first-line’ treatment) for their metastatic colorectal cancer and then continued on Avastin with a different chemotherapy after their cancer progressed (so-called ‘second-line’ treatment) lived significantly longer than people who received only chemotherapy in the second-line setting. No new safety findings were observed and adverse events were consistent with those seen in previous trials of Avastin. Full data from the ML 18147 study will be submitted for presentation at an upcoming medical meeting.