BEVACIZUMAB (BEV) plus CHEMOTHERAPY (CT) BEYOND FIRST PROGRESSION IN PATIENTS (PTS) WITH METASTATIC COLORECTAL CANCER (MCRC) PREVIOUSLY TREATED WITH BEV-BASED THERAPY: OVERALL SURVIVAL SUBGROUP FINDINGS FROM ML18147

ABSTRACT Background ML18147 evaluated the benefit of continuing BEV + standard CT as second-line (2L) treatment for pts with mCRC progressing after first-line (1L) BEV-containing therapy. Here we report results of pre-specified subgroup and exploratory KRAS mutation analyses. Methods Pts with unresectable, histologically confirmed mCRC progressing within 3 mo after discontinuing 1L BEV were randomised to 2L fluoropyrimidine + oxaliplatin or irinotecan (crossed over from 1L) ± BEV (2.5 mg/kg/wk equivalent). The primary endpoint was overall survival (OS). Subgroup analyses for OS were performed using the same statistical method as for the primary analysis. Results 409 pts were randomised to BEV + CT and 411 to CT (1 pt not treated). Median OS was 11.2 mo for BEV + CT vs 9.8 mo for CT (unstratified HR = 0.81; 95% CI 0.69–0.94; p = 0.0062). Subgroup analyses for OS were generally consistent with the overall population (Table). While the treatment effect in female pts appeared to be lower, the treatment-gender interaction test was not statistically significant. Category Subgroup N HR for OS 95% CI All All 819 0.81 0.69–0.94 Gender Female Male 294 525 0.99 0.73 0.77–1.28 0.60–0.88 Age  ≥ 65 y 458 361 0.79 0.83 0.65–0.98 0.66–1.04 ECOG PS 0  ≥ 1 357 458 0.74 0.87 0.59–0.94 0.71–1.06 First-line PFS ≤9 mo  > 9 mo 449 369 0.89 0.73 0.73–1.09 0.58–0.92 First-line chemotherapy Oxaliplatin-based Irinotecan-based 343 476 0.79 0.82 0.62–1.00 0.67–1.00 Time from last BEV dose ≤42 d  > 42 d 630 189 0.82 0.76 0.69–0.97 0.55–1.06 Liver metastases only No Yes 592 226 0.81 0.79 0.67–0.97 0.59–1.05 No. of organs with metastasis 1  > 1 307 511 0.83 0.77 0.64–1.08 0.64–0.94 KRAS mutation data were available from an exploratory analysis in 616 pts (75%); median OS for KRAS wild-type (WT) pts was 15.4 mo for BEV + CT vs 11.1 mo for CT (HR = 0.69, 95% CI 0.53–0.90; p = 0.0052); in KRAS mutant (MT) pts median OS was 10.4 vs 10.0 mo, respectively (HR = 0.92; 95% CI 0.71–1.18; p = 0.4969). Median PFS for KRAS WT pts was 6.4 mo for BEV + CT vs 4.5 mo for CT (HR = 0.61; 95% CI 0.49–0.77; p  Conclusions ML18147 showed that BEV + CT continued beyond progression significantly improves survival vs CT alone. Findings from the subgroup analyses for OS were generally consistent with the overall population. Disclosure J.M. Vieitez de Prado: Involved in corporate-sponsored trials for Roche. D. Arnold: Consultant / Advisory Board: Roche. Honoraria: Roche. Research funding: Roche. R. Greil: Honoraria: Roche Research support: Roche. E.J.D. Van Cutsem: Research funding: Roche. R. von Moos: Consultant/advisory board: Roche. Honoraria: Roche. Research funding: Roche. J. Bennouna: Consultant / advisory board: Roche. Honoraria: Roche. I. Reyes-Rivera: Employed by Genentech Inc. B. Bendahmane: Employed by F. Hoffmann-La Roche. S. Kubicka: Consultant / advisory board: Roche. Honoraria: Roche. All other authors have declared no conflicts of interest.