Section of Medical Oncology, Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, Connecticut.
David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
J Thorac Oncol. 2021 Oct;16(10):1718-1732. doi: 10.1016/j.jtho.2021.05.001. Epub 2021 May 26.
In the KEYNOTE-010 study, pembrolizumab improved overall survival (OS) versus docetaxel in patients with previously treated, advanced NSCLC with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) ≥50% and ≥1%. We report 5-year efficacy and safety follow-up for the KEYNOTE-010 study.
Patients were randomized to pembrolizumab 2 mg/kg or 10 mg/kg once every 3 weeks or docetaxel 75 mg/m once every 3 weeks for up to 35 cycles (2 y). Patients who completed pembrolizumab treatment and subsequently had recurrence could receive second-course pembrolizumab for up to 17 cycles (1 y). Pembrolizumab doses were pooled in this analysis.
A total of 1034 patients were randomized (pembrolizumab, n = 691; docetaxel, n = 343). Median study follow-up was 67.4 months (range: 60.0‒77.9). The hazard ratio (95% confidence interval) for OS was 0.55 (0.44‒0.69) for patients with PD-L1 TPS ≥50% and 0.70 (0.61‒0.80) with PD-L1 TPS ≥1%. The 5-year OS rates for pembrolizumab versus docetaxel were 25.0% versus 8.2% in patients with PD-L1 TPS ≥50% and 15.6% versus 6.5% with PD-L1 TPS ≥1%. Among 79 patients who completed 35 cycles/2 years of pembrolizumab, the OS rate 3 years after completion (∼5 y from randomization) was 83.0%. A total of 21 patients received second-course pembrolizumab; 11 (52.4%) had an objective response after starting the second course and 15 (71.4%) were alive at data cutoff. Exploratory biomarker analysis revealed that higher tissue tumor mutational burden (≥175 mutations per exome) was associated with improved outcomes with pembrolizumab.
Pembrolizumab continued to provide long-term benefit than docetaxel in patients with previously treated advanced NSCLC with PD-L1 TPS ≥50% and ≥1%. Our findings confirm pembrolizumab as a standard-of-care treatment in the second-line or later setting.
在 KEYNOTE-010 研究中，与多西他赛相比，帕博利珠单抗改善了先前治疗的晚期 NSCLC 患者的总生存期（OS），这些患者的程序性死亡配体 1（PD-L1）肿瘤比例评分（TPS）≥50%且≥1%。我们报告 KEYNOTE-010 研究的 5 年疗效和安全性随访结果。
患者随机接受帕博利珠单抗 2mg/kg 或 10mg/kg，每 3 周一次，或多西他赛 75mg/m2，每 3 周一次，最多 35 个周期（2 年）。完成帕博利珠单抗治疗后复发的患者可接受最多 17 个周期（1 年）的第二疗程帕博利珠单抗治疗。在此分析中，帕博利珠单抗剂量进行了合并。
共有 1034 名患者被随机分配（帕博利珠单抗，n=691；多西他赛，n=343）。中位研究随访时间为 67.4 个月（范围：60.0-77.9）。PD-L1 TPS≥50%患者的 OS 风险比（95%置信区间）为 0.55（0.44-0.69），PD-L1 TPS≥1%患者为 0.70（0.61-0.80）。PD-L1 TPS≥50%的患者中，帕博利珠单抗与多西他赛相比，5 年 OS 率为 25.0%与 8.2%；PD-L1 TPS≥1%的患者中，5 年 OS 率为 15.6%与 6.5%。在完成 35 个周期/2 年帕博利珠单抗治疗的 79 名患者中，完成治疗后 3 年（约 5 年随机分组后）的 OS 率为 83.0%。共有 21 名患者接受了第二疗程的帕博利珠单抗治疗；开始第二疗程后，有 11 名（52.4%）患者有客观缓解，15 名（71.4%）患者在数据截止时存活。探索性生物标志物分析显示，组织肿瘤突变负荷较高（≥175 个外显子突变/每外显子）与帕博利珠单抗的疗效改善相关。
与多西他赛相比，帕博利珠单抗在 PD-L1 TPS≥50%和≥1%的先前治疗的晚期 NSCLC 患者中继续提供长期获益。我们的研究结果证实，帕博利珠单抗是二线或以后治疗的标准治疗方法。
