First‐Line XELOX Plus Bevacizumab Followed by XELOX Plus Bevacizumab or Single‐Agent Bevacizumab as Maintenance Therapy in Patients with Metastatic Colorectal Cancer: The Phase III MACRO TTD Study

Purpose. The aim of this phase III trial was to compare the efficacy and safety of bevacizumab alone with those of bevacizumab and capecitabine plus oxaliplatin (XELOX) as maintenance treatment following induction chemotherapy with XELOX plus bevacizumab in the first‐line treatment of patients with metastatic colorectal cancer (mCRC). Patients and Methods. Patients were randomly assigned to receive six cycles of bevacizumab, capecitabine, and oxaliplatin every 3 weeks followed by XELOX plus bevacizumab or bevacizumab alone until progression. The primary endpoint was the progression‐free survival (PFS) interval; secondary endpoints were the overall survival (OS) time, objective response rate (RR), time to response, duration of response, and safety. Results. The intent‐to‐treat population comprised 480 patients (XELOX plus bevacizumab, n = 239; bevacizumab, n = 241); there were no significant differences in baseline characteristics. The median follow‐up was 29.0 months (range, 0–53.2 months). There were no statistically significant differences in the median PFS or OS times or in the RR between the two arms. The most common grade 3 or 4 toxicities in the XELOX plus bevacizumab versus bevacizumab arms were diarrhea, hand–foot syndrome, and neuropathy. Conclusion. Although the noninferiority of bevacizumab versus XELOX plus bevacizumab cannot be confirmed, we can reliably exclude a median PFS detriment >3 weeks. This study suggests that maintenance therapy with single‐agent bevacizumab may be an appropriate option following induction XELOX plus bevacizumab in mCRC patients. 摘要 目的 本项 III 期试验旨在比较一线卡培他滨+奥沙利铂（ XELOX ）+贝伐珠单抗诱导化疗后贝伐珠单抗单药与贝伐珠单抗 +XELOX 维持治疗对转移性结直肠癌（ mCRC ）患者的疗效和安全性。 患者与方法 患者随机接受6个周期的贝伐珠单抗+卡培他滨+奥沙利铂（每3周），继以 XELOX+ 贝伐珠单抗或贝伐珠单抗单药，直至进展。主要终点为无进展生存（PFS）时间；次要终点为总生存（OS）时间、客观缓解率（RR）、至缓解时间、缓解持续时间和安全性。 结果 意向性治疗人群包含480例患者（XELOX+贝伐珠单抗，n=239；贝伐珠单抗，n =241）；基线特征方面无显著差异。中位随访时间为29.0个月（范围，0~53.2个月）。两组的中位PFS或OS时间或RR无显著差异。 XELOX+ 贝伐珠单抗组vs.贝伐珠单抗组最常见的3级或4级毒性为腹泻、手足综合征和神经病变。 结论 尽管无法证实贝伐珠单抗是否不劣于 XELOX+ 贝伐珠单抗，但>3周的中位PFS损害能可靠排除。本研究提示，单药贝伐珠单抗维持治疗可能是 mCRC 患者继 XELOX+ 贝伐珠单抗诱导治疗后的适宜选择。 This phase III trial compared the efficacy and safety of bevacizumab alone with that of bevacizumab and capecitabine plus oxaliplatin (XELOX) as maintenance treatment following induction chemotherapy with XELOX plus bevacizumab in the first‐line treatment of patients with metastatic colorectal cancer. Noninferiority could not be confirmed, but the median progression‐free survival detriment was >3 weeks.