TY - JOUR
T1 - Safety and efficacy of pembrolizumab monotherapy in elderly patients with PD-L1–positive advanced non–small-cell lung cancer
T2 - Pooled analysis from the KEYNOTE-010, KEYNOTE-024, and KEYNOTE-042 studies
AU - Nosaki, Kaname
AU - Saka, H.
AU - Hosomi, Y.
AU - Baas, Paul
AU - de Castro, Gilberto
AU - Reck, Martin
AU - Wu, Yi Long
AU - Brahmer, Julie R.
AU - Felip, Enriqueta
AU - Sawada, Takeshi
AU - Noguchi, K.
AU - Han, Shi Rong
AU - Piperdi, B.
AU - Kush, Debra A.
AU - Lopes, Gilberto
N1 - Funding Information:
Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc. Kenilworth, NJ, USA. We thank the patients and their families and caregivers for participating in the studies, along with all investigators and site personnel. Critical review of the final version of the manuscript was provided by Jonathan Cheng, MD, and additional statistical analysis support was provided by Yue Shentu, PhD, all of Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc. Kenilworth, NJ, USA (MSD). Medical writing and editorial assistance was provided by Charlotte Majerczyk, PhD, of C4 MedSolutions, LLC (Yardley, PA, USA), a CHC Group company. This assistance was funded by MSD.
Funding Information:
Funding for this research was provided by Merck Sharp & Dohme Corp. , a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA . We thank the patients and their families and caregivers for participating in the studies, along with all investigators and site personnel. Critical review of the final version of the manuscript was provided by Jonathan Cheng, MD, and additional statistical analysis support was provided by Yue Shentu, PhD, all of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD). Medical writing and editorial assistance was provided by Charlotte Majerczyk, PhD, of C4 MedSolutions, LLC (Yardley, PA, USA), a CHC Group company. This assistance was funded by MSD.
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/9
Y1 - 2019/9
N2 - 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.
AB - 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.
KW - Chemotherapy
KW - Elderly
KW - Non–small-cell lung cancer
KW - Pembrolizumab
KW - Phase 3
KW - Pooled analysis
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U2 - 10.1016/j.lungcan.2019.07.004
DO - 10.1016/j.lungcan.2019.07.004
M3 - Article
C2 - 31446994
AN - SCOPUS:85069962164
SN - 0169-5002
VL - 135
SP - 188
EP - 195
JO - Lung Cancer
JF - Lung Cancer
ER -
