Safety and efficacy of pembrolizumab monotherapy in elderly patients with PD-L1–positive advanced non–small-cell lung cancer: Pooled analysis from the KEYNOTE-010, KEYNOTE-024, and KEYNOTE-042 studies. (September 2019)

• Record Type: Journal Article
• Authors: Nosaki, Kaname; Saka, Hideo; Hosomi, Yukio; Baas, Paul; de Castro, Gilberto; Reck, Martin; Wu, Yi-Long; Brahmer, Julie R.; Felip, Enriqueta; Sawada, Takeshi; Noguchi, Kazuo; Han, Shi Rong; Piperdi, Bilal; Kush, Debra A.; Lopes, Gilberto
• Is Part Of: Lung cancer. Volume 135(2019)
• Page Start: 188
• Page End: 195
• Publication Date: 2019-09
• Subjects: AE adverse event -- ECOG PS Eastern Cooperative Oncology Group performance score -- ESMO European Society for Medical Oncology -- HR hazard ratio -- JLCS Japan Lung Cancer Society -- NSCLC non–small-cell lung cancer -- OS overall survival -- PD-1 programmed death 1 -- PD-L1 programmed death ligand 1 -- Q3W every 3 weeks -- TPS tumor proportion score; Elderly -- Pembrolizumab -- Non–small-cell lung cancer -- Chemotherapy -- Pooled analysis -- Phase 3; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2019.07.004
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Pooled analysis of elderly patients (≥75 y) from KEYNOTE-010, -024, and -042. Pembrolizumab improved survival vs chemotherapy for PD-L1‒positive advanced NSCLC. No unexpected toxicity with pembrolizumab was observed in elderly patients. Pembrolizumab outcomes in the elderly were consistent with overall study population. Abstract: Objectives: Most lung cancer diagnoses occur in elderly patients, who are underrepresented in clinical trials. We present a pooled analysis of safety and efficacy in elderly patients (≥75 years) who received pembrolizumab (a programmed death 1 inhibitor) for advanced non–small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1)‒positive tumors. Methods: The pooled analysis included patients aged ≥18 years with advanced NSCLC with PD-L1–positive tumors from the KEYNOTE-010 (NCT01905657), KEYNOTE-024 (NCT02142738), and KEYNOTE-042 (NCT02220894) studies. In KEYNOTE-010, patients were randomized to pembrolizumab 2 or 10 mg/kg every 3 weeks (Q3W) or docetaxel, as second- or later-line therapy. In KEYNOTE-024 and KEYNOTE-042, patients were randomized to first-line pembrolizumab 200 mg Q3W or platinum-based chemotherapy. Overall survival (OS) was estimated by the Kaplan-Meier method, and safety data were summarized in elderly patients (≥75 years). Results: The analysis included 264 elderly patients with PD-L1–positive tumors (PD-L1 tumor proportion score [TPS] ≥1%); among these, 132 had PD-L1 TPS ≥ 50%. Pembrolizumab improved OS among elderly patients with PD-L1 TPS ≥ 1% (hazard ratio [HR], 0.76 [95% CI, 0.56–1.02]) and PD-L1 TPS ≥ 50% (HR, 0.40 [95% CI, 0.25–0.64]). Pembrolizumab as first-line therapy also improved OS among elderly patients with PD-L1 TPS ≥ 50% (from KEYNOTE-024 and KEYNOTE-042) compared with chemotherapy (HR, 0.41 [95% CI, 0.23‒0.73]). Pembrolizumab was associated with fewer treatment-related adverse events (AEs) in elderly patients (overall, 68.5% vs 94.3%; grade ≥3, 24.2% vs 61.0%) versus chemotherapy. Immune-mediated AEs and infusion reactions were more common with pembrolizumab versus chemotherapy (overall, 24.8% vs 6.7%; grade 3‒4: 9.4% vs 0%; no grade 5 events). Conclusions: In this pooled analysis of elderly patients with advanced NSCLC with PD-L1‒positive tumors, pembrolizumab improved OS versus chemotherapy, with a more favorable safety profile. Outcomes with pembrolizumab in patients ≥75 years were comparable to those in the overall populations in the individual studies.