O-0020 Bevacizumab + Chemotherapy Beyond First Progression in Metastatic Colorectal Cancer Patients Previously Treated with Bevacizumab-Based Therapy: TML Study Subgroup Findings

Abstract

ABSTRACT Introduction Bevacizumab in combination with fluoropyrimidine-based chemotherapy is a standard treatment for patients with metastatic colorectal cancer (mCRC) in the first-line and bevacizumab-naive second-line settings. This is the first randomised study evaluating the benefit of continuing bevacizumab in combination with standard chemotherapy as second-line treatment for patients with mCRC who progressed after receiving a standard bevacizumab-containing regimen in the first-line setting. Here we report the main study findings and those from planned subgroup analyses. Methods Patients with unresectable, histologically confirmed mCRC who progressed within 3 months after discontinuation of first-line bevacizumab + chemotherapy were randomised to second-line fluoropyrimidine-based chemotherapy ± bevacizumab (2.5 mg/kg/wk equivalent). Choice of oxaliplatin- or irinotecan-based second-line chemotherapy was dependent on the first-line regimen used (crossover); the type of chemotherapy partner was included in the stratification variables. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), response rate and safety. Subgroups analysed included gender, age, ECOG PS, duration of first-line PFS (≤9 months vs >9 months), first-line chemotherapy (oxaliplatin- vs irinotecan-based), time since last bevacizumab treatment (≤42 days vs >42 days), liver-only metastases (no vs yes) and number of organs with metastases (≤1 vs >1). Results The intent-to-treat (ITT) population comprised 409 patients who received bevacizumab + chemotherapy and 411 who were treated with chemotherapy alone. Demographics and baseline disease characteristics of the patients randomised between February 2006 and June 2010 were well balanced between treatment arms. The primary endpoint (improvement in OS) was met; median OS was 11.2 months for bevacizumab + chemotherapy vs 9.8 months for chemotherapy alone (hazard ratio [HR] = 0.81; 95% CI, 0.69–0.94; unstratified log-rank test, p = 0.0062). Median PFS was 5.7 months for bevacizumab + chemotherapy vs 4.1 months for chemotherapy alone (HR = 0.68; 95% CI, 0.59–0.78; unstratified log-rank test, p Conclusion This is the first randomised study to prospectively investigate the impact of continuing bevacizumab treatment in the second-line setting for patients who progressed after receiving a bevacizumab-containing regimen as first-line treatment for mCRC. Our findings demonstrate that bevacizumab + chemotherapy (crossed over from the first-line regimen) continued beyond progression significantly prolongs OS and PFS in the second-line mCRC setting. In the planned subgroup analysis for OS, findings were generally consistent with the overall population. Download : Download full-size image Figure 2 . Subgroup analysis. overall survival in the ITT population (n=820).