Pembrolizumab and Pemetrexed for Older Patients With Nonsquamous NSCLC and Programmed Cell Death-Ligand 1 Tumor Proportion Scores of Less Than 50%

Introduction: Pembrolizumab with pemetrexed and cisplatin/carboplatin is an approved first-line treatment for metastatic nonsquamous NSCLC. Nevertheless, its efficacy and safety in patients aged 75 years and above remain unclear. We assessed the efficacy and safety of pembrolizumab with pemetrexed in patients with programmed cell death-ligand 1 expression tumor proportion scores of less than 50%. Methods: This multicenter, open-label, phase 2 trial involved 42 institutions across Japan. Eligible participants had metastatic or recurrent nonsquamous NSCLC without sensitizing EGFR or ALK alterations, were aged 75 years or above, had a programmed cell death-ligand 1 tumor proportion score of less than 50%, had not undergone systemic chemotherapy, and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received pemetrexed (500 mg/m²) and pembrolizumab (200 mg) on day 1 of each 21-day cycle. The primary endpoint was the objective response rate. The secondary endpoints included progression-free survival, overall survival, and safety. Results: Forty-nine patients were enrolled in this study between July 2020 and May 2022. The objective response rate was 36.7% (95% confidence interval [CI]: 23.4%–51.7%). The disease control rate was 65.3% (95% CI: 50.4–78.3%). The median progression-free survival was 7.6 months (95% CI: 4.8–16.2), and the median overall survival was 19.4 months (95% CI: 11.8 mo–unreached). The most common grade 3 or 4 adverse events were neutropenia (31.3%), leukopenia (20.8%), and anemia (12.5%). No treatment-related deaths occurred during this period. Conclusions: Pembrolizumab with pemetrexed is a promising first-line treatment option for older patients with metastatic nonsquamous NSCLC. This trial was registered at ClinicalTrials.gov (NCT04396457) and the Japan Registry of Clinical Trials (jRCTs041200012).