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 - 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 -
