Outcomes With Pembrolizumab Monotherapy in Patients With Programmed Death-Ligand 1–Positive NSCLC With Brain Metastases: Pooled Analysis of KEYNOTE-001, 010, 024, and 042

Aaron S. Mansfield, MD; Roy S. Herbst, MD, PhD; Gilberto de Castro, Jr., MD, PhD; Rina Hui, MB, BS, PhD; Nir Peled, MD, PhD; Dong-Wan Kim, MD; Silvia Novello, MD, PhD; Miyako Satouchi, MD; Yi-Long Wu, MD; Edward B. Garon, MD; Martin Reck, MD, PhD; Andrew G. Robinson, MD; Ayman Samkari, MD; Bilal Piperdi, MD; Victoria Ebiana, MD; Jianxin Lin, MS; Tony S.K. Mok, MD

JTO Clinical and Research Reports (Aug 2021)

Outcomes With Pembrolizumab Monotherapy in Patients With Programmed Death-Ligand 1–Positive NSCLC With Brain Metastases: Pooled Analysis of KEYNOTE-001, 010, 024, and 042

Aaron S. Mansfield, MD,
Roy S. Herbst, MD, PhD,
Gilberto de Castro, Jr., MD, PhD,
Rina Hui, MB, BS, PhD,
Nir Peled, MD, PhD,
Dong-Wan Kim, MD,
Silvia Novello, MD, PhD,
Miyako Satouchi, MD,
Yi-Long Wu, MD,
Edward B. Garon, MD,
Martin Reck, MD, PhD,
Andrew G. Robinson, MD,
Ayman Samkari, MD,
Bilal Piperdi, MD,
Victoria Ebiana, MD,
Jianxin Lin, MS,
Tony S.K. Mok, MD

Affiliations

Aaron S. Mansfield, MD: Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota; Corresponding author. Address for correspondence: Aaron S. Mansfield, MD, Division of Medical Oncology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905.
Roy S. Herbst, MD, PhD: Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, Connecticut
Gilberto de Castro, Jr., MD, PhD: Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil
Rina Hui, MB, BS, PhD: Westmead Hospital and the University of Sydney, Sydney, Australia
Nir Peled, MD, PhD: Soroka Cancer Center, Ben Gurion University, Beer Sheva, Israel
Dong-Wan Kim, MD: Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea
Silvia Novello, MD, PhD: Azienda Ospedaliero-Universitaria San Luigi Gonzaga, University of Turin, Orbassano, Italy
Miyako Satouchi, MD: Hyogo Cancer Center, Akashi, Japan
Yi-Long Wu, MD: Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangdong, China
Edward B. Garon, MD: David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California
Martin Reck, MD, PhD: Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany
Andrew G. Robinson, MD: Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, Ontario, Canada
Ayman Samkari, MD: Merck & Co., Inc., Kenilworth, New Jersey
Bilal Piperdi, MD: Merck & Co., Inc., Kenilworth, New Jersey
Victoria Ebiana, MD: Merck & Co., Inc., Kenilworth, New Jersey
Jianxin Lin, MS: Merck & Co., Inc., Kenilworth, New Jersey
Tony S.K. Mok, MD: State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, China

Journal volume & issue: Vol. 2, no. 8
p. 100205

Abstract

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Introduction: We retrospectively evaluated outcomes in patients with programmed death-ligand 1 (PD-L1)–positive non–small-cell lung cancer (NSCLC) to determine whether baseline (i.e., at study enrollment) brain metastases were associated with the efficacy of pembrolizumab versus chemotherapy. Methods: We pooled data for patients with previously treated or untreated PD-L1‒positive (tumor proportion score [TPS], ≥1%) advanced or metastatic NSCLC in KEYNOTE-001 (NCT01295827), KEYNOTE-010 (NCT01905657), KEYNOTE-024 (NCT02142738), and KEYNOTE-042 (NCT02220894). Patients received pembrolizumab (2 mg/kg, 10 mg/kg, or 200 mg every 3 wk or 10 mg/kg every 2 wk); chemotherapy was a comparator in all studies except KEYNOTE-001. All studies included patients with previously treated, stable brain metastases. Results: A total of 3170 patients were included, 293 (9.2%) with and 2877 (90.8%) without baseline brain metastases; median (range) follow-up at data cutoff was 12.9 (0.1‒43.7) months. Pembrolizumab improved overall survival versus chemotherapy in patients with or without baseline brain metastases: benefit was seen in patients with PD-L1 TPS ≥50% (0.67 [95% confidence intervals (CI): 0.44‒1.02] and 0.66 [95% CI: 0.58‒0.76], respectively) and PD-L1 TPS ≥1% (0.83 [95% CI: 0.62‒1.10] and 0.78 [95% CI: 0.71‒0.85], respectively). Progression-free survival was improved, objective response rates were higher, and duration of response was longer with pembrolizumab versus chemotherapy regardless of brain metastasis status. The incidence of treatment-related adverse events with pembrolizumab versus chemotherapy was 66.3% versus 84.4% in patients with brain metastases and 67.2% versus 88.3% in those without. Conclusions: Pembrolizumab monotherapy improved outcomes and was associated with fewer adverse events than chemotherapy in patients with treatment-naive and previously treated PD-L1‒positive advanced/metastatic NSCLC regardless of the presence of baseline treated, stable brain metastases.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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