Bintrafusp alfa and chemotherapy as first-line treatment in biliary tract cancer: A randomized phase 2/3 trial.

approach_and_results

This randomized, double-blind, placebo-controlled, adaptive design phase 2/3 trial (NCT04066491) included adults who are treatment-naive with locally advanced/metastatic biliary tract cancer.

这项随机、双盲、安慰剂对照、自适应设计的2/3期临床试验（NCT04066491）纳入了局部晚期/转移性胆道癌的成年初治患者。

Patients (N = 297) were randomized to receive an IV infusion of BA (2400 mg once/3 wk) plus GemCis (gemcitabine 1000 mg/m 2 +cisplatin 25 mg/m 2 on days 1 and 8/3 wk; 8 cycles) (BA group, n = 148) or placebo+GemCis (placebo group, n = 149).

患者（N = 297）被随机分配接受静脉输注BA（2400 mg，每3周一次）加GemCis（吉西他滨1000 mg/m^2 +顺铂25 mg/m^2，在第1天和第8天/3周；共8个周期）（BA组，n = 148）或安慰剂+GemCis（安慰剂组，n = 149）。

The primary end point was overall survival(OS).

主要终点是总生存（OS）。

For adaptation analysis (phase 2-phase 3; data cutoff: May 20, 2021), efficacy was assessed in the first 150 patients who were antibiotic-naive when 80 progression-free survivalevents had occurred and ≥ 19 weeks of follow-up had been completed (BA, n = 73; placebo, n = 77).

适应性分析（第2阶段-第3阶段；数据截止日期：2021年5月20日），在80个无进展生存事件发生且完成≥19周随访的前150名患者中评估了疗效（BA组，n=73；安慰剂组，n=77）。

Median OS (95% CI) for the BA (11.5 mo [9.3-not estimable]) and placebo (11.5 mo [10.0-not estimable]) groups was comparable (hazard ration 1.23 [95% CI 0.66-2.28]; p = 0.7394); OS data maturity was 27.2% (41 events/151 patients).

BA组（11.5个月[9.3-无法估计]）和安慰剂组（11.5个月[10.0-无法估计]）的中位总生存期（95%置信区间）相当（风险比1.23[95%置信区间0.66-2.28]；p=0.7394）；总生存数据成熟度为27.2%（41个事件/151名患者）。

The most common grade ≥3 treatment-related adverse eventwas anemia (BA, 26.0%; placebo, 22.8%).

最常见的3级或更高级别的治疗相关不良事件是贫血（BA组，26.0%；安慰剂组，22.8%）。

Bleeding adverse events were reported more frequently in the BA group (28.8%) versus the placebo group (7.4%).

与安慰剂组（7.4%）相比，BA组报告的出血不良事件更为频繁（28.8%）。

Deaths within 60 days of the first dose were reported in 7.5% and 1.3% of patients in the BA and placebo groups, respectively.

首次剂量后60天内，BA组和安慰剂组分别有7.5%和1.3%的患者报告死亡。

Conclusions

BA+GemCis did not provide a clinically meaningful benefit compared with GemCis alone as first-line treatment for biliary tract cancer, and the study was discontinued early (terminated: August 20, 2021).

与单独使用GemCis作为胆道癌一线治疗相比，BA+GemCis并未提供临床上有意义的益处，因此研究提前终止（终止日期：2021年8月20日）。