Medical Oncology Unit, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Universita' Cattolica del Sacro Cuore, Rome, Italy.
Medical Oncology Unit, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Universita' Cattolica del Sacro Cuore, Rome, Italy.
Cancer Treat Rev. 2021 Jun;97:102202. doi: 10.1016/j.ctrv.2021.102202. Epub 2021 Mar 30.
The real impact of bevacizumab maintenance as single agent in metastatic colorectal cancer (mCRC) remains unclear. SAKK-41/06 and PRODIGE-9 failed to demonstrate the non-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.
Bibliography electronic databases (PubMed, MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials) were searched for English published 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 start of induction and maintenance. Univariate and multivariate analyses for PFS and OS were performed.
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 progressed during induction and starting maintenance phase entered the analysis. 909 patients were included, 457 (50%) received bevacizumab maintenance. Median PFS from induction start 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.
Despite the statistically significant PFS improvement for bevacizumab maintenance, the absolute benefit appears limited. Subgroup analysis shows a differential effect of bevacizumab maintenance in favor of RAS wild-type patients. Considering these results, maintenance therapy with fluoropyrimidine with or without bevacizumab remains the first option. Single agent bevacizumab maintenance can be considered in selected cases, such as cumulative toxicity or patient's refusal, in particular for RAS wild-type patients.
贝伐单抗单药维持治疗在转移性结直肠癌（mCRC）中的实际影响仍不清楚。SAKK-41/06 和 PRODIGE-9 分别未能证明贝伐单抗维持治疗与不维持治疗相比的非劣效性和优越性，而 AIO-KRK-0207 则表明维持治疗贝伐单抗与贝伐单抗联合氟嘧啶用于策略失败时间的非劣效性。
检索了PubMed、MEDLINE、Embase、Scopus、Web of Science 和 Cochrane 对照试验中心注册库等英文出版的临床研究电子文献数据库，前瞻性随机分配 mCRC 患者在一线化疗加贝伐单抗后接受贝伐单抗维持治疗或不接受。所有纳入试验的研究者均提供了个体患者数据（IPD）。主要终点为无进展生存期（PFS）和总生存期（OS），均从诱导开始和维持开始。对 PFS 和 OS 进行了单变量和多变量分析。
纳入了三项 III 期研究-PRODIGE-9、AIO-KRK-0207 和 SAKK-41/06。考虑到随机分组的不同时间，未在诱导期进展且开始维持期的患者的 IPD 纳入分析。共纳入 909 例患者，其中 457 例（50%）接受贝伐单抗维持治疗。贝伐单抗组和无维持组从诱导开始的中位 PFS 分别为 9.6 个月和 8.9 个月（HR 0.78；95%CI：0.68-0.89；p<0.0001）。亚组分析显示，RAS 状态存在显著的交互作用（p=0.048），维持治疗的获益仅限于 RAS 野生型患者。OS 无差异。
尽管贝伐单抗维持治疗的 PFS 有统计学意义的改善，但绝对获益似乎有限。亚组分析显示，贝伐单抗维持治疗对 RAS 野生型患者有不同的效果。考虑到这些结果，氟嘧啶联合或不联合贝伐单抗的维持治疗仍然是首选。对于累积毒性或患者拒绝等特定情况，如 RAS 野生型患者，可以考虑单药贝伐单抗维持治疗。
