Pembrolizumab in Patients with Advanced Metastatic Germ Cell Tumors

Abstract

Lessons Learned: Background: Advanced germ cell tumors are associated with poor prognosis. We investigated the role of pembrolizumab in patients with advanced germ cell tumors. Methods: We analyzed a prespecified cohort of an open-label, phase II clinical trial in which patients with advanced germ cell tumors were treated with pembrolizumab (200 mg) intravenously every 21 days. The endpoints of the study were the non-progression rate (NPR) at 27 weeks, safety, and tolerability. An NPR >20% was considered successful and worthy of further pursuit. Results: From August 2016 to February 2018, 12 patients (10 men, 2 women) were treated (median age, 35 years [range, 22–63 years]; median number of prior systemic therapies, 3.5 [range, 2–7]; median number of metastatic sites, 3 [range, 2–8]). Overall, pembrolizumab was well tolerated. One patient experienced both grade 1 immune-related skin rash and grade 3 immune-related pneumonitis. No patient died from toxicity. Three patients had radiographic stable disease that lasted for 10.9 months, 5.5 months, and 4.5 months, respectively. No objective response was noted. The median progression-free survival was 2.4 months (95% confidence interval [CI], 1.5–4.5 months), and the median overall survival was 10.6 months (95% CI, 4.6–27.1 months). The 27-week NPR was 9.0% (95% CI, 0.23–41.2%). Conclusion: Overall, pembrolizumab was safe and had limited antitumor activity in these patients. In the advanced, metastatic setting, tumor profiling to understand the mechanisms of resistance to immunotherapy and innovative clinical trials to identify efficacious combination regimens rather than off-label use of pembrolizumab are warranted.