Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial
Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial
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DOI：
10.1001/jamaoncol.2020.3370
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发表时间：
2020-10-01
期刊：
影响因子：
28.4
通讯作者：
Tabernero, Josep
中科院分区：
文献类型：
--
作者：
Shitara, Kohei;Van Cutsem, Eric;Tabernero, Josep
重要性针对未经治疗的晚期胃/胃食管交界处（G/GEJ）癌症的安全有效疗法仍然未得到满足。目的评估帕博利珠单抗、帕博利珠单抗加化疗或单独化疗对未经治疗的晚期胃/胃食管交界处（G/GEJ）癌症患者的抗肿瘤活性。程序性细胞死亡配体1（PD-L1）联合阳性评分（CP 5）大于或等于。设计、设置。3期KEYNOTE-062随机、对照、部分盲法干预性试验在2015年9月18日至2017年5月26日期间从29个国家的200个中心招募了763名PD-L1 CPS ≥ 1的未经治疗、局部晚期/不可切除或转移性G/GEJ癌症患者。1至派姆单抗200 mg，派姆单抗+化疗（顺铂80 mg/m2/d，第1天+氟尿嘧啶800 mg/m2/d，第1 - 5天或卡培他滨1000 mg/m2，每日2次）或化疗+安慰剂，主要终点是PD-L1 CPS大于或等于10的患者的总生存期（OS）和无进展生存期（PFS）。RE.5）.K.TS共有763名患者被随机分配接受派姆单抗（n = 256）、派姆单抗加化疗（n = 257）或化疗（n = 250）。研究队列中所有患者的中位（范围）年龄为62（20-87）岁; 763例患者中有554例（72.6%）为男性。最终分析时，在中位（范围）随访29.4（22.0-41.3）个月后，在CPS ≥ 1/4的患者中，帕博利珠单抗的OS非劣效于化疗（中位，10.6 vs 11.1个月;风险比[HR]，0.91; 99.2% CI，0.69-1]8）。在CPS ≥ 10的患者中，Pembrolizumab单药治疗并不上级于化疗。在CPS ≥ 10的患者中，与化疗相比，Pembrolizumab延长了OS（中位数，17.4 vs 10.8个月; HR，0.69; 95% CI，0.49-0.97），但未对该差异进行统计学检验。在CP 5 ≥ 1/2的患者中，派姆单抗联合化疗的OS并不上级于化疗（12.5 vs 11.1个月; HR，0.85; 95% CI，0.70-1.03; P =.05）或CP 5 ≥ 10（12.3 vs 10.8个月; HR，0.85; 95% CI，0.62-1.17; P =.16）或CPS ≥ 1/4患者的PFS（6.9 vs 6.4个月; HR，0.84; 95% CI，0.70-1.02; P =.04）。Pembrolizumab，Pembrolizumab加化疗和化疗的3至5级治疗相关不良事件发生率分别为17%，73%和69%，分别为CONCLUSIONS AND RELEVANCE这3期随机临床试验发现，在未经治疗的晚期G/GEJ癌症患者中，Pembrolizumab非劣于化疗，观察到的不良事件较少。派姆单抗或派姆单抗加化疗在OS和PFS终点方面并不上级化疗。
IMPORTANCE Safe and effective therapies for untreated, advanced gastric/gastroesophageal junction (G/GEJ) cancer remain an unmet need.OBJECTIVE To evaluate the antitumor activity of pembrolizumab, pembrolizumab plus chemotherapy, or chemotherapy alone in patients with untreated, advanced G/GEJ cancer with programmed cell death ligand l(PD-L1) combined positive score (CP5) of lor greater.DESIGN, SETTING. AND PARTICIPANTS The phase 3 KEYNOTE -062 randomized, controlled, partially blinded interventional trial enrolled 763 patients with untreated, locally advanced/unresectable or metastatic G/GEJ cancer with PD-L1CPS of lor greater from 200 centers in 29 countries between September 18, 2015, and May 26, 2017.INTERVENTIONS Patients were randomized 1:1:1to pembrolizumab 200 mg, pembrolizumab plus chemotherapy (cisplatin 80 mg/m2/d on day 1plus fluorouracil 800 mg/m2/d on days 1 to 5 or capecitabine 1000 mg/m2twice daily), or chemotherapy plus placebo, every 3 weeks.MAIN OUTCOME ABD MEASURES Primary end points were overall survival (OS) and progression -free survival (PFS) in patients with PD-L1CPS of lor greater or 10 or greater. RE.5).K.Ts A total of 763 patients were randomized to pembrolizumab (n = 256), pembrolizumab plus chemotherapy (n = 257), or chemotherapy (n = 250). The median (range) age of all patients in the study cohort was 62 (20-87) years; 554 of 763 (72.6%) were men. At final analysis, after a median (range) follow-up of 29.4 (22.0-41.3) months, pembrolizumab was noninferior to chemotherapy for OS in patients with CPS of lor greater (median, 10.6 vs 11.1months; hazard ratio [HR], 0.91; 99.2% CI, 0.69-1]8). Pembrolizumab monotherapy was not superior to chemotherapy in patients with CPS of lor greater. Pembrolizumab prolonged OS vs chemotherapy in patients with CPS of 10 or greater (median, 17.4 vs 10.8 months; HR, 0.69; 95% CI, 0.49-0.97), but this difference was not statistically tested. Pembrolizumab plus chemotherapy was not superior to chemotherapy for OS in patients with CP5 of lor greater (12.5 vs 11.1 months; HR, 0.85; 95% CI, 0.70-1.03; P =.05) or CP5 of 10 or greater (12.3 vs 10.8 months; HR, 0.85; 95% CI, 0.62-1.17; P =.16) or for PFS in patients with CPS of lor greater (6.9 vs 6.4 months; HR, 0.84; 95% Cl, 0.70-1.02; P =.04). Grade 3 to 5 treatment-related adverse event rates for pembrolizumab, pembrolizumab plus chemotherapy, and chemotherapy were 17%, 73%, and 69%, respectively.CONCLUSIONS AND RELEVANCE This phase 3 randomized clinical trial found that among patients with untreated, advanced G/GEJ cancer, pembrolizumab was noninferior to chemotherapy, with fewer adverse events observed. Pembrolizumab or pembrolizumab plus chemotherapy was not superior to chemotherapy for the OS and PFS end points tested.