Vallejo Jonathon, Singh Harpreet, Larkins Erin, Drezner Nicole, Ricciuti Biagio, Mishra-Kalyani Pallavi, Tang Shenghui, Beaver Julia A, Awad Mark M
Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
Oncology Center of Excellence, US Food and Drug Administration, Silver Spring, MD, USA.
Oncologist. 2024 May 3;29(5):422-430. doi: 10.1093/oncolo/oyae006.
Programmed death ligand 1 (PD-L1) expression is recognized as a key biomarker in the treatment of non-small cell lung cancer (NSCLC) with anti-PD(L)1 inhibitors. Previous work has highlighted that outcomes in patients with NSCLC treated with anti-PD(L)1 inhibitors generally improve with increasing PD-L1 expression. The objectives of these analyses are to quantitate the effect of PD-L1 expression on outcomes, to characterize the potentially nonlinear relationship between PD-L1 expression and outcomes, and to assess potential differences in these relationships across subgroups.
We performed a retrospective, pooled analysis of 11 clinical trials submitted to the US FDA between 2015 and 2022 that included patients with advanced NSCLC treated with anti-programmed death 1 or anti-PD-L1 immune checkpoint inhibitor (ICI) monotherapy in the first-line (1L) or second-line (2L) treatment setting. The clinical outcomes explored were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).
The primary analysis population included 3806 patients with advanced NSCLC, of which 2040 were treated in 1L and 1766 in 2L. For patients with a PD-L1 score of 100% in the 1L setting, the hazard ratio versus a patient with 1% PD-L1 was 0.55 (95% CI, 0.43 to 0.70) for OS and 0.50 (95% CI, 0.41 to 0.61) for PFS. For patients with a PD-L1 score of 100% in the 2L setting, the hazard ratio versus a patient with 0% PD-L1 was 0.55 (95% CI, 0.43 to 0.71) for OS and 0.51 (95% CI, 0.41 to 0.63) for PFS. Subgroup analyses suggested that this relationship may vary by subgroup, particularly by region.
These analyses suggest PD-L1 expression has an appreciable impact on clinical outcomes for patients with NSCLC treated with ICI. As the impact of PD-L1 expression on outcomes may vary across regions, it is critical that future trials are multiregional and enroll a diverse patient population.
程序性死亡配体1（PD-L1）表达被认为是使用抗PD（L）1抑制剂治疗非小细胞肺癌（NSCLC）的关键生物标志物。先前的研究强调，使用抗PD（L）1抑制剂治疗的NSCLC患者的预后通常随着PD-L1表达的增加而改善。这些分析的目的是量化PD-L1表达对预后的影响，描述PD-L1表达与预后之间潜在的非线性关系，并评估各亚组之间这些关系的潜在差异。
我们对2015年至2022年期间提交给美国食品药品监督管理局（FDA）的11项临床试验进行了回顾性汇总分析，这些试验纳入了在一线（1L）或二线（2L）治疗中接受抗程序性死亡1或抗PD-L1免疫检查点抑制剂（ICI）单药治疗的晚期NSCLC患者。所探讨的临床结局为总生存期（OS）、无进展生存期（PFS）和客观缓解率（ORR）。
主要分析人群包括3806例晚期NSCLC患者，其中2040例接受1L治疗，1766例接受2L治疗。在1L治疗组中，PD-L1评分100%的患者与PD-L1为1%的患者相比，OS的风险比为0.55（95%CI，0.43至0.70），PFS的风险比为0.
