Impact of Clinicopathologic Features on the Efficacy of PD-1/PD-L1 Inhibitors in Patients With Previously Treated Non-small-cell Lung Cancer

Abstract

Background: The current study aimed to comprehensively investigate the impact of various clinicopathologic features on the efficacy of programmed cell death-1 (PD-1) and ligand (PD-L1) inhibitors in patients with previously treated non-small-cell lung cancer (NSCLC).

Patients and methods: Randomized controlled trials that compared PD-1/PD-L1-inhibitor monotherapy with chemotherapy or placebo in patients with previously treated NSCLC were included.

Results: Five trials were included (n = 3025). For all studies, PD-1/PD-L1 inhibitors significantly prolonged overall survival (OS) (hazard ratio [HR], 0.70; P < .001) and progression-free survival (PFS) versus chemotherapy (HR, 0.86; P = .020). Subgroup analysis showed that anti-PD-1/PD-L1 monotherapy could markedly improve OS in elderly patients (HR, 0.69; P < .001), female patients (HR, 0.70; P < .001), never-smoking patients (HR, 0.73; P = .001), and patients with a histology of squamous cell carcinoma (HR, 0.67; P < .001), but not PFS in the elderly and female patient groups. Notably, PD-1/PD-L1 inhibitors cannot prolong both OS (HR, 0.76; P = .390) and PFS (HR, 0.74; P = .210) in patients with central nervous system (CNS) metastasis, whereas patients without CNS metastasis could benefit from anti-PD-1/PD-L1 monotherapy on OS (HR, 0.71; P < .001).

Conclusion: PD-1/PD-L1-inhibitor monotherapy could significantly prolong both OS and PFS in patients with previously treated NSCLC. Subgroup analyses showed that most patients including elderly, females, never-smokers, and patients with squamous cell carcinomas do benefit. However, whether patients with CNS metastasis could benefit from anti-PD-1/PD-L1 monotherapy requires further validation.

Keywords: Clinical parameter; Immune checkpoint; Immunotherapy; NSCLC; Survival.