| Resum: |
The RAISE phase III trial demonstrated ramucirumab + FOLFIRI improved survival compared with placebo + FOLFIRI for second-line metastatic colorectal carcinoma patients previously treated with first-line bevacizumab, oxaliplatin, and a fluoropyrimidine. Analyses reported here found similar efficacy and safety in patients regardless of KRAS mutational status, time to first-line progression, and age. The RAISE phase III clinical trial demonstrated that ramucirumab + FOLFIRI improved overall survival (OS) [hazard ratio (HR) = 0. 844, P = 0. 0219] and progression-free survival (PFS) (HR = 0. 793, P < 0. 0005) compared with placebo + FOLFIRI for second-line metastatic colorectal carcinoma (mCRC) patients previously treated with first-line bevacizumab, oxaliplatin, and a fluoropyrimidine. Since some patient or disease characteristics could be associated with differential efficacy or safety, prespecified subgroup analyses were undertaken. This report focuses on three of the most relevant ones: KRAS status (wild-type versus mutant), age (<65 versus ≥65 years), and time to progression (TTP) on first-line therapy (<6 versus ≥6 months). OS and PFS were evaluated by the Kaplan-Meier analysis, with HR determined by the Cox proportional hazards model. Treatment-by-subgroup interaction was tested to determine whether treatment effect was consistent between subgroup pairs. Patients with both wild-type and mutant KRAS benefited from ramucirumab + FOLFIRI treatment over placebo + FOLFIRI (interaction P = 0. 526); although numerically, wild-type KRAS patients benefited more (wild-type KRAS : median OS = 14. 4 versus 11. 9 months, HR = 0. 82, P = 0. 049; mutant KRAS : median OS = 12. 7 versus 11. 3 months, HR = 0. 89, P = 0. 263). Patients with both longer and shorter first-line TTP benefited from ramucirumab (interaction P = 0. 9434), although TTP <6 months was associated with poorer OS (TTP ≥6 months: median OS = 14. 3 versus 12. 5 months, HR = 0. 86, P = 0. 061; TTP <6 months: median OS = 10. 4 versus 8. 0 months, HR = 0. 86, P = 0. 276). The subgroups of patients ≥65 versus <65 years also derived a similar ramucirumab survival benefit (interaction P = 0. 9521) (≥65 years: median OS = 13. 8 versus 11. 7 months, HR = 0. 85, P = 0. 156; <65 years: median OS = 13. 1 versus 11. 9 months, HR = 0. 86, P = 0. 098). The safety profile of ramucirumab + FOLFIRI was similar across subgroups. These analyses revealed similar efficacy and safety among patient subgroups with differing KRAS mutation status, longer or shorter first-line TTP, and age. Ramucirumab is a beneficial addition to second-line FOLFIRI treatment for a wide range of patients with mCRC. ClinicalTrials. gov, NCT01183780. |
visitant ::
identificació
(National Cancer Center Hospital East (Japan))
