Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India.
Department of Medical Oncology, Homi Bhabha Cancer Hospital, Varanasi, India.
J Clin Oncol. 2024 Sep 20;42(27):3218-3227. doi: 10.1200/JCO.23.02420. Epub 2024 Aug 5.
Patients with chemotherapy-responsive advanced biliary tract cancers (BTCs) are usually observed after 6 months of gemcitabine-based therapy. There is limited prospective evidence for maintenance strategies after chemotherapy.
This investigator-initiated, open-label, randomized, integrated phase II-III study enrolled adult patients with advanced BTC from two cancer centers in India. Patients with histologically confirmed advanced biliary tract adenocarcinoma who had at least disease stabilization after 6 months of gemcitabine-based chemotherapy were randomly assigned (1:1) to either active surveillance or switch maintenance, which was a combination of bevacizumab 5 mg/kg intravenous once every 21 days plus erlotinib 100 mg once daily. Both arms were continued until disease progression, unacceptable toxicity, or patient decision to withdraw. The primary end point of the phase II component of the trial was investigator-evaluated progression-free survival. This trial is registered with Clinical Trials Registry of India (CTRI/2019/05/019323I).
From May 2021 to November 2022, 98 patients were randomly assigned to active surveillance (n = 49) or bevacizumab-erlotinib (n = 49). A majority of patients had gallbladder cancer (80%). The median follow-up was 13.4 months. The median progression-free survival was 3.1 months (95% CI, 2.47 to 3.64) in the active surveillance group versus 5.3 months (95% CI, 3.53 to 7.04) in the bevacizumab-erlotinib group (hazard ratio, 0.51 [95% CI, 0.33 to 0·74]; = .0013). The most common grade 3 class-specific adverse events associated with bevacizumab-erlotinib were acneiform rash 1 (2%) and oral stomatitis 1 (2%) with erlotinib and bleeding 1 (2%) with bevacizumab.
The combination of bevacizumab and erlotinib as switch maintenance improves progression-free survival with an acceptable safety profile compared with active surveillance in patients with advanced BTCs in this phase II study. The trial moves on to the phase III component to evaluate improvement in overall survival.
化疗缓解的晚期胆道癌（BTC）患者通常在接受基于吉西他滨的治疗 6 个月后进行观察。化疗后维持治疗的前瞻性证据有限。
这是一项由研究者发起的、开放标签、随机、整合的 II/III 期研究，在印度的两个癌症中心招募了晚期 BTC 成年患者。组织学证实的晚期胆道腺癌患者，在接受基于吉西他滨的化疗至少 6 个月后至少疾病稳定，随机（1:1）分配至主动监测或转换维持治疗，后者是贝伐珠单抗 5 mg/kg 静脉注射，每 21 天一次，联合厄洛替尼 100 mg 每日一次。两个治疗组均持续到疾病进展、不可接受的毒性或患者决定退出。试验的 II 期部分的主要终点是研究者评估的无进展生存期。该试验在印度临床试验注册中心（CTRI/2019/05/019323I）注册。
从 2021 年 5 月至 2022 年 11 月，98 名患者被随机分配至主动监测（n=49）或贝伐珠单抗-厄洛替尼（n=49）组。大多数患者患有胆囊癌（80%）。中位随访时间为 13.4 个月。主动监测组的中位无进展生存期为 3.1 个月（95%CI，2.47 至 3.64），贝伐珠单抗-厄洛替尼组为 5.3 个月（95%CI，3.53 至 7.04）（风险比，0.51 [95%CI，0.33 至 0.74]； =.0013）。与贝伐珠单抗-厄洛替尼相关的最常见的 3 级特定类别不良事件是痤疮样皮疹 1 例（2%）和口腔黏膜炎 1 例（2%）（厄洛替尼）和出血 1 例（2%）（贝伐珠单抗）。
在这项 II 期研究中，与主动监测相比，贝伐珠单抗和厄洛替尼联合作为转换维持治疗可提高晚期 BTC 患者的无进展生存期，且安全性可接受。该试验进入 III 期部分以评估总生存期的改善。
