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

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2019-09, Vol.135, p.188-195
• Main 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
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents, Immunological - administration & dosage; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - mortality; Chemotherapy; Elderly; Female; Humans; Lung Neoplasms - diagnosis; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - mortality; Male; Mutation; Neoplasm Staging; Non–small-cell lung cancer; Pembrolizumab; Phase 3; Pooled analysis; Randomized Controlled Trials as Topic; Treatment Outcome
• ISSN: 0169-5002; 1872-8332; 1872-8332
• DOI: 10.1016/j.lungcan.2019.07.004

•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. 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. 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). 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). 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.