First-Line Anti–PD-(L)1 Therapy with or without Chemotherapy for Advanced PD-L1–High NSCLC: FDA Pooled Analysis

Advances in cancer immunotherapy have led to the development and approval of innovative immune checkpoint inhibitors (ICIs) that stimulate an anticancer immune response. ICIs that target PD-L1 demonstrated efficacy in patients with advanced non–small-cell lung cancer (NSCLC) as monotherapy and in combination with other therapeutic modalities.¹ The US Food and Drug Administration (FDA) has approved ICIs with or without chemotherapy to treat patients with PD-L1–high advanced NSCLC in the first-line setting; however, the clinical benefit of these regimens has not been well-established in this population.²

This study analyzed pooled data from 12 randomized controlled trials that investigated anti–PD-(L)1 regimens with or without chemotherapy to treat patients with advanced NSCLC in the first-line setting. PD-L1 score was measured based on the proportion of tumor cells stained by the assay, and analysis was conducted for patients with tumor PD-L1 scores ≥50%.² Using a pooled analysis, the study compared overall survival (OS), progression-free survival (PFS), and overall response rate between chemoimmunotherapy and immunotherapy alone. Median survival times were estimated using Kaplan-Meier methods, and hazard ratios (HRs) using Cox proportional hazards models stratified by trial. In addition, odds ratios were calculated using a logistic regression model with trial as a covariate. All analyses were adjusted for age, sex, race, Eastern Cooperative Oncology Group (ECOG) performance status, histology, and smoking status.²

The study included 3189 patients with NSCLC and PD-L1 scores ≥50%. Of the enrolled patients, 38% were aged 65 to 74 years, with ECOG scores of ≥1. In addition, 89% were former or current smokers. The median OS in the pooled chemoimmunotherapy (chemo-IO; n = 455) and immunotherapy-only (I-O; n = 1298) arms was 25.0 months compared with 20.9 months (HR, 0.82; 95% confidence interval [CI], 0.62-1.08); median PFS was 9.6 months versus 7.1 months, respectively (HR, 0.69; 95% CI, 0.55-0.87). The overall response rate was higher with chemo-IO than with I-O (61% vs 43%; odds ratio, 1.2; 95% CI, 1.1-1.3).²

The researchers concluded that most patients with PD-L1 scores ≥50% treated with FDA-approved chemoimmunotherapy regimens had OS and PFS outcomes comparable to or better than patients treated with ICI monotherapy. Importantly, elderly patients aged ≥75 years did not achieve improved outcomes with chemoimmunotherapy compared with ICI monotherapy. These findings highlight the importance of shared decision-making and consideration of patient factors that affect tolerability.

References

1. Onoi K, Chihara Y, Uchino J, et al. Immune checkpoint inhibitors for lung cancer treatment: a review. J Clin Med. 2020;9:1362.
2. Akinboro O, Vallejo JJ, Nakajima EC, et al. Outcomes of anti–PD-(L)1 therapy with or without chemotherapy (chemo) for first-line (1L) treatment of advanced non–small cell lung cancer (NSCLC) with PD-L1 score ≥ 50%: FDA pooled analysis. Presented at: 2022 American Society of Clinical Oncology Annual Meeting; June 3-7, 2022. Abstract 9028; Chicago, IL. Abstract 9000.