Bevacizumab (BEV) plus chemotherapy (CT) continued beyond first disease progression (PD) in patients with metastatic colorectal cancer (mCRC) previously treated with BEV-based therapy: Outcomes according to KRAS status and first-line CT backbone in the ML18147 study.
520 Background: ML18147 is the first randomized phase III study to show that continuing BEV + standard CT as second-line (2L) treatment significantly improves overall survival (OS) and progression-free survival (PFS) in patients with mCRC who progressed after receiving a standard first-line (1L) BEV-containing regimen. Here we report an exploratory analysis of outcomes based on CT backbone and KRAS status. Methods: Patients with unresectable, histologically confirmed mCRC who progressed ≤3 months after discontinuing 1L BEV were randomised to 2L CT (crossed over from oxaliplatin to irinotecan and vice versa) ± BEV. This post-hoc analysis evaluated OS, PFS, overall response rate (ORR) and disease control rate (DCR) according to 1L CT backbone (irinotecan- or oxaliplatin-based) and KRAS status (Scorpion ARMS test for KRAS codons 12 and 13). Results: In total, 616 patients (75% of the ITT population) were included in this analysis; 316 had wild-type (WT) and 300 had mutant-type (MT) KRAS status; 355 received 1L irinotecan and 261 received 1L oxaliplatin. BEV+CT beyond PD prolonged OS and PFS vs CT alone, regardless of whether oxaliplatin- or irinotecan-based CT was used in the 1L and whether patients had WT or MT KRAS (Table). Adverse events were not increased when continuing BEV+CT beyond PD and were consistent with previous findings. Conclusions: This post hoc analysis suggests that continuing BEV + 2L oxaliplatin or irinotecan-based CT (following crossover) leads to prolonged OS and PFS, regardless of KRAS status or if oxaliplatin or irinotecan-based CT was used in the 1L. Clinical trial information: NCT00700102. [Table: see text]