Camrelizumab plus CAPOX with camrelizumab based maintenance versus CAPOX alone as initial treatment for gastric or gastro-oesophageal junction adenocarcinoma: randomised phase 3 trial.

Methods

Randomised, open label, phase 3 study.

随机、开放标签、第三阶段研究。

75 hospitals in China, 13 March 2019 to 16 August 2021.

75家中国医院，2019年3月13日至2021年8月16日。

885 adults (≥18 years) with previously untreated, human epidermal growth factor receptor 2 (HER2) negative, unresectable, locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma.

885名年龄≥18岁的成年患者，之前未接受过治疗，人类表皮生长因子受体2（HER2）阴性，无法切除的局部晚期或转移性胃癌或胃食管交界处腺癌。

Patients were randomised (2:2:1) to receive camre+CAPOX followed by camre+apa, CAPOX only, or camre+CAPOX followed by camre, stratified by Eastern Cooperative Oncology Group performance status, peritoneal metastasis, and programmed death ligand 1 (PD-L1) combined positive score.

患者被随机分配（2:2:1）接受camre+CAPOX后camre+apa、仅CAPOX或camre+CAPOX后camre治疗，根据东部肿瘤协作组（ECOG）表现状态、腹膜转移和程序性死亡配体1（PD-L1）联合阳性评分进行分层。

Assignment to camre+CAPOX followed by camre was introduced midway through enrolment.

在招募过程中，中途引入了camre+CAPOX后camre的分配方案。

The primary endpoint was overall survivalfor camre+CAPOX followed by camre+apa versus CAPOX alone in the PD-L1 positive population (combined positive score >1) and the overall population who received at least one dose of study drug.

主要终点是PD-L1阳性人群（联合阳性评分>1）和至少接受一次研究药物的总体人群中，camre+CAPOX后接camre+apa与仅CAPOX治疗的总生存比较。

Comparisons of camre+CAPOX followed by camre versus CAPOX alone and of camre+CAPOX followed by camre+apa versus camre+CAPOX-camre were descriptive.

camre+CAPOX后接camre与仅CAPOX治疗的比较，以及camre+CAPOX后接camre+apa与camre+CAPOX-camre的比较，均为描述性比较。

Safety was assessed in all patients who received at least one dose of study drug.

所有接受至少一剂研究药物的患者均进行了安全性评估。

Results

352 patients received camre+CAPOX followed by camre+apa, 349 received CAPOX alone, and 177 received camre+CAPOX followed by camre.

352名患者接受了camre+CAPOX随后是camre+apa治疗，349名患者仅接受了CAPOX治疗，另外177名患者接受了camre+CAPOX随后是camre治疗。

At the time of data cut off, 454 of 592 (76.7%) deaths had occurred in the PD-L1 positive population and 709 of 878 (80.8%) in the overall population.

截止到数据截止时，在PD-L1阳性人群中，454例中的592例（76.7%）发生了死亡，而在整个研究人群中，709例中的878例（80.8%）发生了死亡。

Overall survivalwas longer with camre+CAPOX followed by camre+apa than with CAPOX alone in the PD-L1 positive population (median 15.0 v 12.5 months; hazard ratio0.80 (95% CI 0.65 to 0.98); one sided P=0.02) and in the overall population (median 13.5 v 12.1 months; hazard ratio0.80 (0.68 to 0.94); one sided P=0.004).

在PD-L1阳性人群中，与单独使用CAPOX相比，联合使用camre+CAPOX和camre+apa的总生存期更长（中位生存期分别为15.0个月和12.5个月；风险比为0.80（95%置信区间0.65至0.98）；单侧P值为0.02），在整个人群中也是如此（中位生存期分别为13.5个月和12.1个月；风险比为0.80（95%置信区间0.68至0.94）；单侧P值为0.004）。

Use of camre+CAPOX followed by camre also showed longer overall survivalversus CAPOX in the PD-L1 positive population (median 15.3 v 12.5 months; hazard ratio0.76 (0.58 to 0.97); one sided nominal P=0.01) and overall population (median 14.2 v 12.1 months; hazard ratio0.80 (0.65 to 0.98); one sided nominal P=0.02).

在PD-L1阳性人群中，卡莫司汀+CAPOX后接卡莫司汀治疗组的总生存期显著长于仅使用CAPOX的治疗组（中位生存期分别为15.3个月和12.5个月；风险比0.76（95%置信区间0.58至0.97）；单侧名义P值为0.01）。在整体人群中，卡莫司汀+CAPOX后接卡莫司汀治疗组的总生存期也显著长于仅使用CAPOX的治疗组（中位生存期分别为14.2个月和12.1个月；风险比0.80（95%置信区间0.65至0.98）；单侧名义P值为0.02）。

No overall survivalbenefit was observed with camre+CAPOX followed by camre+apa versus camre+CAPOX followed by camre.

在卡莫司汀+CAPOX后接卡莫司汀+apa与卡莫司汀+CAPOX后接卡莫司汀的治疗方案比较中，并未观察到总生存期的显著益处。

Treatment related adverse events of grade ≥3 occurred in 239 of 352 (67.9%) patients in the camre+CAPOX followed by camre+apa group, 158 of 349 (45.3%) in the CAPOX alone group, and 83 of 177 (46.9%) in the camre+CAPOX followed by camre group.

在camre+CAPOX后接camre+apa组的352名患者中，有239名（67.9%）发生了3级或以上的治疗相关不良事件，在仅接受CAPOX组的349名患者中，有158名（45.3%）发生了3级或以上的不良事件，在camre+CAPOX后接camre组的177名患者中，有83名（46.9%）发生了3级或以上的不良事件。

Conclusions

Initial treatment with camrelizumab plus CAPOX followed by camrelizumab based maintenance was associated with longer overall survivalthan CAPOX alone in human epidermal growth factor receptor 2 (HER2) negative, unresectable, locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma.

与仅接受CAPOX治疗相比，以camrelizumab联合CAPOX治疗后接camrelizumab为基础的维持治疗，与HER2阴性、不可切除的局部晚期或转移性胃癌或胃食管交界处腺癌患者的总生存期延长相关。

Exploratory comparisons between the two camrelizumab based regimens showed no additional survival benefit, with higher rates of treatment related adverse events of grade ≥3 and treatment discontinuations when apatinib was added during maintenance.

两种基于卡瑞利珠单抗的方案的探索性比较显示，在维持治疗期间添加阿帕替尼并未带来额外的生存益处，反而导致了更高比例的3级或更高级别的治疗相关不良事件和治疗中断。

trial_registration

ClinicalTrials.gov NCT03813784.

ClinicalTrials.gov NCT03813784。