帕博丽珠单抗联合化疗治疗鳞状非小细胞肺癌癌症：KEYNOTE-407三期研究的5年更新

SCI

12 February 2023

Pembrolizumab Plus Chemotherapy in Squamous Non–Small-Cell Lung Cancer: 5-Year Update of the Phase III KEYNOTE-407 Study

(Journal of Clinical Oncology, IF: 50.717)

Silvia Novello, Dariusz M. Kowalski, Alexander Luft, Mahmut Gumus¸ David Vicente, Julien Mazieres, Jeronimo Rodrıguez-Cid, Ali Tafreshi, Ying Cheng, Ki Hyeong Lee, Alexander Golf, Shunichi Sugawara, Andrew G. Robinson, Balazs Halmos, Erin Jensen, Paul Schwarzenberger, M. Catherine Pietanza, and Luis Paz-Ares

CORRESPONDENCE TO: silvia.novello@unito.it 

Abstract 摘要  

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

临床试验通常包括在不同时间成熟的多个终点。初始报告（通常基于主要终点）可在关键计划的共同主要或次要分析尚不可用时发布。临床试验更新报告提供了一个传播JCO或其他地方发布的研究的结果的机会，并且主要终点已经报告。

We report 5-year efficacy and safety outcomes from the phase III KEYNOTE-407 study (ClinicalTrials.gov identifier: NCT02775435). Eligible patients with previously untreated, metastatic squamous non–small-cell lung cancer (NSCLC) were randomly assigned 1:1 to pembrolizumab 200 mg or placebo plus carboplatin and paclitaxel/nab-paclitaxel once every 3 weeks for four cycles, followed by pembrolizumab or placebo for up to 35 cycles. Primary end points were overall survival (OS) and progression-free survival (PFS) per RECIST version 1.1 by blinded independent central review (BICR). Five hundred fifty-nine patients were randomly assigned in the intention-to-treat population (pembrolizumab plus chemotherapy, n=278; placebo plus chemotherapy, n=281). The median time from random assignment to data cutoff was 56.9 (range, 49.9-66.2) months. OS and PFS were improved with pembrolizumab plus chemotherapy versus placebo plus chemotherapy (hazard ratio [95% CI], 0.71 [0.59 to 0.85] and 0.62 [0.52 to 0.74]), with 5-year OS rates of 18.4% versus 9.7%, respectively. Toxicity was manageable. Among 55 patients who completed 35 cycles of pembrolizumab, the objective response rate was 90.9% and the 3-year OS rate after completion of 35 cycles (approximately 5 years after random assignment) was 69.5%. Pembrolizumab plus chemotherapy maintained an OS and PFS benefit versus placebo plus chemotherapy in previously untreated, metastatic squamous NSCLC and is a standard-of-care first-line treatment option for metastatic squamous NSCLC regardless of programmed death ligand 1 expression.

我们报告了三期KEYNOTE-407研究的5年疗效和安全性结果（ClinicalTrials.gov标识符：NCT02775435）。符合条件的先前未经治疗的转移性鳞状非小细胞肺癌（NSCLC）患者按照1:1比例随机分为帕博丽珠单抗组和对照组，其中帕博丽珠单抗组每4个周期，每3周服用一次200 mg 帕博丽珠单抗，对照组使用安慰剂联合卡铂和紫杉醇/nab-紫杉醇，随后服用帕博丽珠单抗或安慰剂，最多服用35个周期。主要终点是根据RECIST 1.1版通过盲法独立中心审查（BICR）得出的总生存率（OS）和无进展生存率（PFS）。五百五十九名患者被随机分配到意向治疗人群中（帕博丽珠单抗+化疗，n=278；安慰剂+化疗，n=281）。从随机分配到数据截止的中位时间为56.9（范围49.9-66.2）个月。与安慰剂加化疗相比，帕博丽珠单抗加化疗可改善OS和PFS（风险比[95%CI]，0.71[0.59至0.85]和0.62[0.52至0.74]），5年OS率分别为18.4%和9.7%。毒性是可控的。在55名完成了35个周期帕博丽珠单抗治疗的患者中，客观有效率为90.9%，完成35个周期（随机分配后约5年）后的3年OS率为69.5%。帕博丽珠单抗联合化疗与安慰剂联合化疗相比，在先前未治疗的转移性鳞状NSCLC中维持较好的OS和PFS获益，因此无论程序性死亡配体1表达如何，帕博丽珠单抗联合化疗是转移性鳞状NSCLC的标准治疗一线治疗选择。

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