BEVACIZUMAB (BEV) plus CHEMOTHERAPY (CT) BEYOND FIRST PROGRESSION IN PATIENTS (PTS) WITH METASTATIC COLORECTAL CANCER (MCRC) PREVIOUSLY TREATED WITH FIRST-LINE BEV plus CT (ML18147): EFFICACY AND SAFETY ANALYSES BY OXALIPLATIN VS IRINOTECAN-BASED CT

ABSTRACT Background ML18147 is the first randomised study to show that continuing BEV + standard CT as second-line (2L) treatment significantly improves overall survival (OS) and progression-free survival (PFS) in pts with mCRC who progressed after receiving a standard first-line (1L) BEV-containing regimen. Here we evaluate outcome in the 2L setting using, as a stratification factor, 1L oxaliplatin vs irinotecan-based CT. Methods Pts with unresectable, histologically confirmed mCRC who progressed within 3 months of discontinuing 1L BEV were randomised to 2L fluoropyrimidine-based CT ± BEV (2.5 mg/kg/wk equivalent). Choice of 2L oxaliplatin or irinotecan was dependent on the 1L regimen (crossover). OS, PFS, overall response rate (ORR) and adverse events (AEs) were analysed in the 2L setting using the 1L oxaliplatin or irinotecan-based CT as a stratification factor. Results 820 pts were randomised from Feb 2006 to Jun 2010. Of these, 343 received 1L oxaliplatin-based CT and 476 received 1L irinotecan-based CT, after which they crossed over to receive either oxaliplatin or irinotecan-based CT in 2L. BEV + CT beyond progression prolonged OS and PFS, regardless of whether oxaliplatin or irinotecan-based CT was used in 1L (Table). ORR was low in CT and BEV + CT-treated pts in both groups. AEs associated with BEV were generally similar in pts treated with either oxaliplatin or irinotecan-based CT. 1L oxaliplatin-based CT 1L irinotecan-based CT Outcome in 2L CT (n = 174) BEV + CT (n = 169) CT (n = 236) BEV + CT (n = 240) Median OS, months 10.0 12.0 9.3 10.9 p-value 0.0524 0.0454 HR (95% CI) 0.79 (0.62–1.00) 0.82 (0.67–1.00) Median PFS, months 4.2 6.2 3.8 5.4 p-value 0.0005 HR (95% CI) 0.68 (0.55–0.85) 0.67 (0.56–0.81) ORR, % 2.9 5.5 4.7 5.4 p-value 0.2414 0.7145 Grade 3–5 AEs in >1% of pts, % Any 52 66 60 61 Hypertension 0 1 2 2 Bleeding/haemorrhage 3 0 1 GI perforation 2 1 Venous thromboembolic event 5 7 1 3 Conclusions This post-hoc subgroup analysis suggests that continuing BEV + 2L oxaliplatin or irinotecan-based CT (following crossover) leads to prolonged OS and PFS, regardless of the type of oxaliplatin or irinotecan-based CT used 1L. Disclosure P. Osterlund: Consultant / advisory board: Roche Honoraria: Roche. T. Andre: Consultant / advisory board: Roche. J. Sastre: Honoraria: Roche Research funding: Roche. R. Greil: Honoraria: Roche Research support: Roche. S. Kubicka: Consultant / advisory board: Roche. Honoraria: Roche. I. Reyes-Rivera: Employed by Genentech Inc. B. McCall: Employed by Genentech Inc. E.J.D. Van Cutsem: Research funding: Roche. All other authors have declared no conflicts of interest.