O-0021 Randomised Phase III Study of Bevacizumab + Chemotherapy Beyond Progression in Bevacizumab-Treated Patients with Metastatic Colorectal Cancer: TML Study Kras 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 randomised study evaluated the benefit of continuing bevacizumab 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. The study included a broad biomarker collection as an exploratory objective. We present here analysis of outcomes according to tumour KRAS status. 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). The choice of oxaliplatin- or irinotecan-based second-line chemotherapy was based on the regimen used in the first-line setting (crossover) and was included in the stratification variables. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), response rate and safety. Subgroup analysis according to KRAS status was performed for both OS and PFS; no adjustment was made for multiplicity. Results Conclusive tumour KRAS mutation data were available for 616 of the 820 patients (75%). Baseline characteristics were similar in the biomarker and randomised populations. Overall, 300 (49%) patients had mutant-type (MT) KRAS tumours and 316 (51%) had wild-type (WT) KRAS tumours. Median OS in the KRAS WT group was 15.4 months for bevacizumab + chemotherapy vs 11.1 months for chemotherapy alone (p = 0.0052; HR = 0.69) and 10.4 months for bevacizumab + chemotherapy vs 10.0 months for chemotherapy alone in the KRAS MT group (p = 0.4969; HR = 0.91). Median PFS in the KRAS WT group was 6.4 months for bevacizumab + chemotherapy vs 4.5 months for chemotherapy alone (p Conclusion This is the first randomized 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. The biomarker findings from this study suggest that patients with both WT and MT KRAS tumours are likely to benefit from bevacizumab treatment.