Pembrolizumab in brain metastases of diverse histologies: phase 2 trial results.

Abstract

Brain metastases (BMs) are an emerging challenge in oncology due to increasing incidence and limited treatments. Here, we present results of a single-arm, open-label, phase 2 trial evaluating intracranial efficacy of pembrolizumab, a programmed cell death protein 1 inhibitor, in 9 patients with untreated BMs (cohort A) and 48 patients with recurrent and progressive BMs (cohort B) across different histologies. The primary endpoint was the proportion of patients achieving intracranial benefit, defined by complete response, partial response or stable disease. The primary endpoint was met with an intracranial benefit rate of 42.1% (90% confidence interval (CI): 31-54%). The median overall survival, a secondary endpoint, was 8.0 months (90% CI: 5.5-8.7 months) across both cohorts, 6.5 months (90% CI: 4.5-18.7 months) for cohort A and 8.1 months (90% CI: 5.3-9.6 months) for cohort B. Seven patients (12.3%), encompassing breast, melanoma and sarcoma histologies, had overall survival greater than 2 years. Thirty patients (52%; 90% CI: 41-64%) had one or more grade-3 or higher adverse events that were at least possibly treatment related. Two patients had grade-4 adverse events (cerebral edema) that were deemed at least possibly treatment related. These results suggest that programmed cell death protein 1 blockade may benefit a select group of patients with BMs, and support further studies to identify biomarkers and mechanisms of resistance. ClinicalTrials.gov identifier: NCT02886585.

• Authors: Priscilla K Brastianos, Albert E Kim, Anita Giobbie-Hurder, Eudocia Q Lee, Nancy U Lin, Beth Overmoyer, Patrick Y Wen, Lakshmi Nayak, Justine V Cohen, Jorg Dietrich, April Eichler, Rebecca S Heist, Ian Krop, Donald Lawrence, Jennifer Ligibel, Sara Tolaney, Erica Mayer, Eric Winer, Brittany Bent, Magali A de Sauvage, Nazanin Ijad, Juliana M Larson, Braxton Marion, Sally Nason, Naina Murthy, Sherry Ratcliff, Elizabeth J Summers, Maura Mahar, Helen A Shih, Kevin Oh, Daniel P Cahill, Elizabeth R Gerstner, Ryan J Sullivan
• Journal: Nature medicine (Nat Med) Vol. 29 Issue 7 Pg. 1728-1737 (07 2023) ISSN: 1546-170X [Electronic] United States
• PMID: 37268724 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.

Chemical References

• Antibodies, Monoclonal, Humanized
• pembrolizumab

Topics

• Humans
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols
• Brain Neoplasms (drug therapy, secondary)
• Melanoma (pathology)