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 Brahmer, Enriqueta Felip, Takeshi Sawada, K. Noguchi, Shi Rong Han, B. Piperdi, Debra A. Kush, Gilberto Lopes

Research output: Contribution to journalArticle

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 1 2019

Fingerprint

Non-Small Cell Lung Carcinoma
Safety
Ligands
Neoplasms
Drug Therapy
Survival
docetaxel
pembrolizumab
Platinum
Lung Neoplasms
Therapeutics
Clinical Trials

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

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

In: Lung Cancer, Vol. 135, 01.09.2019, p. 188-195.

Research output: Contribution to journalArticle

Nosaki, Kaname ; Saka, H. ; Hosomi, Y. ; Baas, Paul ; de Castro, Gilberto ; Reck, Martin ; Wu, Yi Long ; Brahmer, Julie ; Felip, Enriqueta ; Sawada, Takeshi ; Noguchi, K. ; Han, Shi Rong ; Piperdi, B. ; Kush, Debra A. ; Lopes, Gilberto. / 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. In: Lung Cancer. 2019 ; Vol. 135. pp. 188-195.
@article{f81473b11194474a96b20fb3cf67b599,
title = "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",
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.",
keywords = "Chemotherapy, Elderly, Non–small-cell lung cancer, Pembrolizumab, Phase 3, Pooled analysis",
author = "Kaname Nosaki and H. Saka and Y. Hosomi and Paul Baas and {de Castro}, Gilberto and Martin Reck and Wu, {Yi Long} and Julie Brahmer and Enriqueta Felip and Takeshi Sawada and K. Noguchi and Han, {Shi Rong} and B. Piperdi and Kush, {Debra A.} and Gilberto Lopes",
year = "2019",
month = "9",
day = "1",
doi = "10.1016/j.lungcan.2019.07.004",
language = "English (US)",
volume = "135",
pages = "188--195",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",

}

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

AU - Felip, Enriqueta

AU - Sawada, Takeshi

AU - Noguchi, K.

AU - Han, Shi Rong

AU - Piperdi, B.

AU - Kush, Debra A.

AU - Lopes, Gilberto

PY - 2019/9/1

Y1 - 2019/9/1

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

UR - http://www.scopus.com/inward/record.url?scp=85069962164&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069962164&partnerID=8YFLogxK

U2 - 10.1016/j.lungcan.2019.07.004

DO - 10.1016/j.lungcan.2019.07.004

M3 - Article

VL - 135

SP - 188

EP - 195

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

ER -