Bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: a meta-analysis of individual patients’ data from 3 phase III studies
Menée à partir des données de trois essais de phase III incluant 909 patients atteints d'un cancer colorectal de stade métastatique, cette étude évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, du bévacizumab en traitement d'entretien après un traitement de première ligne combinant chimiothérapie et bévacizumab
Background : The real impact of bevacizumab maintenance as single agent in metastatic colorectalcancer (mCRC) remains unclear. SAKK-41/06 and PRODIGE-9 failed to demonstrate thenon-inferiority and superiority of bevacizumab versus no maintenance, respectively,while AIO-KRK-0207 showed the non-inferiority of maintenance bevacizumab versus bevacizumab and fluoropyrimidines for time to strategy failure. Methods : Bibliography electronic databases (PubMed, MEDLINE, Embase, Scopus, Web of Science,and the Cochrane Central Register of Controlled Trials) were searched for Englishpublished clinical trials prospectively randomizing mCRC patients to receive bevacizumab maintenance or not after first-line chemotherapy plus bevacizumab. Individual patients’ data (IPD) were provided by investigators for all included trials. Primary end-points were progression-free survival (PFS) and overall survival (OS), both from the startof induction and maintenance. Univariate and multivariate analyses for PFS and OSwere performed. Results : Three phase III studies - PRODIGE-9, AIO-KRK-0207 and SAKK-41/06 – were included.Considering the different timing of randomization, IPD of patients not progressedduring induction and starting maintenance phase entered the analysis. 909 patientswere included, 457 (50%) received bevacizumab maintenance. Median PFS from inductionstart was 9.6 and 8.9 months in bevacizumab group versus no maintenance group, respectively(HR 0.78; 95%CI: 0.68-0.89; p<0.0001). Subgroups analysis for PFS showed a significant interaction according for RAS status (p=0.048), with a maintenance benefit limited to RAS wild-type patients. No difference in terms of OS was observed. Conclusions : Despite the statistically significant PFS improvement for bevacizumab maintenance,the absolute benefit appears limited. Subgroup analysis shows a differential effectof bevacizumab maintenance in favor of RAS wild-type patients. Considering these results, maintenance therapy with fluoropyrimidinewith or without bevacizumab remains the first option. Single agent bevacizumab maintenancecan be considered in selected cases, such as cumulative toxicity or patient’s refusal,in particular for RAS wild-type patients.