medwireNews: The addition of pembrolizumab to enzalutamide has “modest activity” against metastatic castration-resistant prostate cancer (mCRPC) that has become resistant to enzalutamide, say the KEYNOTE-199 researchers.
Presenting results from cohorts 4 and 5 of the phase 2 trial, comprising men with RECIST-measurable and bone-predominant disease, respectively, Julie Graff (OHSU Knight Cancer Institute, Portland, Oregon, USA) noted that the combination appeared to have antitumor activity in both groups.
As reported at the 2020 Genitourinary Cancers Symposium in San Francisco, California, USA, all participants were required to have had a clinically meaningful response to enzalutamide before experiencing disease progression, and they could have received prior abiraterone.
Among the 81 men in cohort 4, treatment with pembrolizumab 200 mg every 3 weeks plus enzalutamide led to an objective response rate of 12% (2% complete, 10% partial) over a median follow-up of 15.3 months. An additional 38% had stable disease, giving a disease control rate (DCR) of 51%. The median duration of response was 6.3 months.
Fifty-three percent of men had a decrease in target lesion size from baseline, with 24% experiencing a reduction of at least 30%.
The 45 men in cohort 5 were followed up for a median of 19.1 months and achieved a DCR – defined as non-complete response and non-progressive disease – of 51% with the combination.
Radiographic progression-free survival was a median of 4.2 months in cohort 4 and 4.4 months in cohort 5, with 12-month rates of 17% and 23%, respectively. The median overall survival time was unreached in cohort 4 and was 18.8 months in cohort 5, and a respective 70% and 75% of participants were alive at 12 months.
Altogether, treatment-related adverse events (AEs) of grade 3 or worse occurred in 25% of the 126 men in the two cohorts, while immune-mediated AEs of the same severity were observed in 15%. Two patients in cohort 4 died as a result of an immune-mediated AE – one case each of Guillain–Barré syndrome and myasthenia gravis.
Graff pointed out that the incidence of rash of any grade or of grade 3–4 was “higher than previously reported for individual agents,” but only one patient needed intravenous steroids. The remaining cases were managed with oral or topical steroids or needed no intervention, she said.
“The addition of pembrolizumab to enzalutamide after enzalutamide resistance showed modest antitumor activity and durable response,” and “the combination had a manageable safety profile,” the presenter summarized.
She concluded that pembrolizumab–enzalutamide is now being evaluated in the phase 3 KEYNOTE-641 trial enrolling men who are enzalutamide-naïve.
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2020 Genitourinary Cancers Symposium; San Francisco, California, USA: 13–15 February