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

doi:10.1016/j.jtocrr.2021.100205

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

JTO Clin Res Rep. 2021 Jul 1;2(8):100205. doi: 10.1016/j.jtocrr.2021.100205. eCollection 2021 Aug.

Authors

Aaron S Mansfield¹, Roy S Herbst², Gilberto de Castro Jr³, Rina Hui⁴, Nir Peled⁵, Dong-Wan Kim⁶, Silvia Novello⁷, Miyako Satouchi⁸, Yi-Long Wu⁹, Edward B Garon¹⁰, Martin Reck¹¹, Andrew G Robinson¹², Ayman Samkari¹³, Bilal Piperdi¹³, Victoria Ebiana¹³, Jianxin Lin¹³, Tony S K Mok¹⁴

Affiliations

¹ Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
² Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, Connecticut.
³ Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil.
⁴ Westmead Hospital and the University of Sydney, Sydney, Australia.
⁵ Soroka Cancer Center, Ben Gurion University, Beer Sheva, Israel.
⁶ Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
⁷ Azienda Ospedaliero-Universitaria San Luigi Gonzaga, University of Turin, Orbassano, Italy.
⁸ Hyogo Cancer Center, Akashi, Japan.
⁹ Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangdong, China.
¹⁰ David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California.
¹¹ Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany.
¹² Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, Ontario, Canada.
¹³ Merck & Co., Inc., Kenilworth, New Jersey.
¹⁴ State Key Laboratory of Translational Oncology, Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region, China.

Abstract

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.

Keywords: Brain metastases; Chemotherapy; Non‒small-cell lung cancer; PD-L1; Pembrolizumab.

Grants and funding

UL1 TR001863/TR/NCATS NIH HHS/United States