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Bevacizumab (BEV) + 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

2012; Elsevier BV; Volume: 23; Linguagem: Inglês

10.1016/s0923-7534(20)33175-6

1569-8041

José María Viéitez de Prado, Christophe Borg, Dirk Arnold, Richard Greil, E.J.D. Van Cutsem, Roger von Moos, Jaafar Bennouna, Irmarie Reyes‐Rivera, Belguendouz Bendahmane, Stefan Kubicka,

Cancer Genomics and Diagnostics

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. 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. 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.CategorySubgroupNHR for OS95% CIAllAll8190.810.69–0.94GenderFemaleMale2945250.990.730.77–1.280.60–0.88Age 9 mo4493690.890.730.73–1.090.58–0.92First-line chemotherapyOxaliplatin-basedIrinotecan-based3434760.790.820.62–1.000.67–1.00Time from last BEV dose≤42 d > 42 d6301890.820.760.69–0.970.55–1.06Liver metastases onlyNoYes5922260.810.790.67–0.970.59–1.05No. of organs with metastasis1 > 13075110.830.770.64–1.080.64–0.94KRAS 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 < 0.0001); in KRAS MT pts median PFS was 5.5 vs 4.1 mo, respectively (HR = 0.70; 95% CI 0.56–0.89; p = 0.0027). No treatment interaction by KRAS status was seen for OS (p = 0.1266) or PFS (p = 0.4436). 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 < 0.0001); in KRAS MT pts median PFS was 5.5 vs 4.1 mo, respectively (HR = 0.70; 95% CI 0.56–0.89; p = 0.0027). No treatment interaction by KRAS status was seen for OS (p = 0.1266) or PFS (p = 0.4436). 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. 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.