Anti–PD-L1 Therapy in Combination with Chemotherapy versus Immunotherapy Alone in First-Line NSCLC with PD-L1 Score 1% to 49%

Chemotherapy plus immunotherapy (IO) may improve efficacy outcomes over IO alone in most patients with advanced non–small-cell lung cancer (NSCLC) and programmed death ligand 1 (PD-L1) scores between 1% and 49%.

Approved regimens for the first-line treatment of metastatic non–small-cell lung cancer (NSCLC) include immunotherapy (IO) plus chemotherapy ± anti-angiogenesis inhibitors. IO-only therapy is approved only for PD-L1–positive NSCLC. Patients with PD-L1 scores between 1% and 49% have many therapeutic options, and little is known about how subgroups of patients in this cohort benefit from available treatment regimens.1

To investigate this, data were pooled from 8 randomized controlled trials that investigated anti–PD-L1 therapy as IO-only or in chemotherapy plus IO regimens for the first-line treatment of patients with advanced NSCLC. PD-L1 score was defined as the proportion of tumor cells stained by the assay, and analysis was conducted for patients whose tumors had PD-L1 scores between 1% and 49%. Tumor-infiltrating immune cell staining was not considered. Overall survival (OS) and progression-free survival (PFS) were compared between chemo-IO and IO alone via a pooled analysis. Median survival times were estimated using Kaplan–Meier methods. Hazard ratios were estimated using Cox proportional hazards models stratified by trial and adjusted for age, sex, race, Eastern Cooperative Oncology Group (ECOG), histology, and smoking status.1

A total of 2108 patients with advanced NSCLC and PD-L1 scores between 1% and 49% were identified for this analysis.1 At baseline, 37% of patients were between the ages of 65 and 74 years, while 12% were aged ≥75 years.1 Most were male (67%) and white (79%) with an ECOG performance status of ≥1 (65%).1 Most of these patients were also smokers (85%).1 Median follow-up time was 12.1 months.1

This pooled analysis showed that the 639 patients with advanced NSCLC and PD-L1 scores between 1% and 49% who received chemo-IO had longer PFS and OS compared with 529 patients treated with IO alone.1 Median PFS results for the 2 groups were 7.7 months and 4.2 months, respectively (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.48-0.76).1 Median OS was 21.4 months compared with 14.5 months (HR, 0.68; 95% CI, 0.52-0.90). Researchers noted that results should be considered exploratory and hypothesis-generating.1

Researchers believe that this exploratory pooled analysis suggests that chemo-IO may improve efficacy outcomes compared with IO alone in most subgroups of patients with advanced NSCLC who have PD-L1 scores between 1% and 49%. Patients who were aged ≥75 years experienced similar outcomes across therapeutic options.1


1. Akinboro O, Vallejo JJ, Mishra-Kalyani PS, et al. Outcomes of anti-PD-(L1) therapy in combination with chemotherapy versus immunotherapy (IO) alone for first-line (1L) treatment of advanced non-small cell lung cancer (NSCLC) with PD-L1 score 1-49%: FDA pooled analysis. Presented at: 2021 American Society of Clinical Oncology (ASCO) Annual Meeting; June 4-8, 2021. Abstract 9001.