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

Kaname Nosaki, H. Saka, Y. Hosomi, Paul Baas, Gilberto de Castro, Martin Reck, Yi Long Wu, Julie R. Brahmer, Enriqueta Felip, Takeshi Sawada, K. Noguchi, Shi Rong Han, B. Piperdi, Debra A. Kush, Gilberto Lopes

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5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)188-195
Number of pages8
JournalLung Cancer
Volume135
DOIs
StatePublished - Sep 2019

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Keywords

  • Chemotherapy
  • Elderly
  • Non–small-cell lung cancer
  • Pembrolizumab
  • Phase 3
  • Pooled analysis

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Nosaki, K., Saka, H., Hosomi, Y., Baas, P., de Castro, G., Reck, M., Wu, Y. L., Brahmer, J. R., Felip, E., Sawada, T., Noguchi, K., Han, S. R., Piperdi, B., Kush, D. A., & Lopes, G. (2019). 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. Lung Cancer, 135, 188-195. https://doi.org/10.1016/j.lungcan.2019.07.004