In a phase II study reported in the Journal of Clinical Oncology,¹ Matthew D. Galsky, MD, of The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, and colleagues found that maintenance pembrolizumab produced additional responses and improved progression-free survival vs placebo in patients with metastatic urothelial cancer who had at least stable disease on first-line platinum-based chemotherapy.

Matthew D. Galsky, MD

Study Details

In the U.S. investigator-initiated double-blind trial, 108 patients with at least stable disease on first-line chemotherapy were randomly assigned between December 2015 and November 2018 to receive 200 mg of pembrolizumab once every 3 weeks (n = 55) or placebo (n = 53) for up to 24 months. Patients with disease progression on placebo could cross over to receive pembrolizumab. The primary outcome measure was progression-free survival.

Outcomes

Among 43 patients treated with pembrolizumab and 42 treated with placebo without a complete response on chemotherapy, an objective response was observed in 23% of those receiving pembrolizumab and 10% of those receiving placebo, including a complete response in 9% vs 0%. Median progression-free survival was 5.4 months in the pembrolizumab group vs 3.0 months in the placebo group (hazard ratio [HR] = 0.65, P =.04).

Median overall survival was 22 months vs 18.7 months (HR = 0.91, 95% confidence interval = 0.52–1.59). Among 27 patients treated with placebo who crossed over to pembrolizumab after disease progression, the objective response rate was 22%, the median progression-free survival after crossover was 2.7 months, and the median overall survival after crossover was 15.8 months.

Among patients with available data, PD-L1 combined positive score (CPS) was at least 10 in 30% of patients treated with pembrolizumab and 30% of patients treated with placebo. No significant interactions between PD-L1 CPS ≥ 10 and treatment group were observed for progression-free survival (P = .5) or overall survival (P = .9).

Toxicity

Grade 3 or 4 adverse events occurred in 59% of patients (grade 4 in 15%) of the pembrolizumab group vs 38% (all grade 3) of the placebo group. Immune-related adverse events requiring systemic steroid treatment occurred in 20% of patients initially randomly assigned to treatment with pembrolizumab. One patient in the pembrolizumab group died due to a treatment-related adverse event (hepatitis).

The investigators concluded: “Switch maintenance pembrolizumab leads to additional objective responses in patients achieving at least stable disease with first-line platinum-based chemotherapy and prolongs progression-free survival in patients with metastatic urothelial cancer.” 

Disclosure: The study was supported by Merck and a National Cancer Institute grant to The Tisch Cancer Institute. For full disclosures of the study authors, visit ascopubs.org. Dr. Galsky has stock or other ownership interests in Rappta Therapeutics; has served in a consulting/advisory role for BioMotiv, Janssen, Dendreon, Merck, GlaxoSmithKline, Lilly, Astellas Pharma, Genentech, Bristol Myers Squibb, Novartis, Pfizer, EMD Serono, AstraZeneca, Seattle Genetics, Incyte, Aileron Therapeutics, Dracen Pharmaceuticals, Inovio Pharmaceuticals, NuMab, and Dragonfly Therapeutics; has received institutional research funding from Janssen Oncology, Dendreon, Novartis, Bristol Myers Squibb, Merck, AstraZeneca, and Genentech/Roche; and has patents, royalties, or other intellecutal property related to methods and compositions for treating cancer (Mount Sinai School of Medicine, July 2012, application number 20120322792).

REFERENCE

1. Galsky MD, Mortazavi A, Milowsky MI, et al: Randomized double-blind phase II study of maintenance pembrolizumab versus placebo after first-line chemotherapy in patients with metastatic urothelial cancer. J Clin Oncol 38:1797-1806, 2020.