In the phase II KEYNOTE-199 study, reported in the Journal of Clinical Oncology by Antonarakis et al, pembrolizumab showed activity and had an acceptable safety profile in patients with treatment-refractory metastatic castration-resistant prostate cancer.

Study Details

The trial was conducted at 85 sites in 21 countries. A total of 258 patients who had prior treatment with docetaxel and one or more targeted endocrine therapies were enrolled between July 2016 and March 2017 into three cohorts: 133 patients with programmed cell death ligand 1 (PD-L1)-positive disease (cohort 1), 66 with PD-L1–negative disease (cohort 2), and 59 with bone-predominant disease irrespective of PD-L1 expression (cohort 3).

Patients received 200 mg of pembrolizumab every 3 weeks for up to 35 cycles. The primary endpoint was objective response rate, based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, on central review in cohorts 1 and 2.

Responses

Objective response was observed in seven patients (5%) in cohort 1—including complete response in two—and two patients (3%) in cohort 2. Median durations of response in cohorts 1 and 2 were not reached (range = 1.9–≥ 21.8 months) and 10.6 months (range = 4.4–16.8 months).

Disease control rates were 10%, 9%, and 22% in cohorts 1, 2, and 3, respectively. Median overall survival was 9.5 months, 7.9 months, and 14.1 months in the three cohorts, with estimated 1-year survival rates of 41%, 35%, and 62%.

Adverse Events

Overall, treatment-related adverse events of any grade occurred in 60% of patients, with the most common being fatigue (15%), diarrhea (11%), and decreased appetite (10%). Treatment-related adverse events led to discontinuation of treatment in 5% of patients.

Treatment-related grade ≥ 3 adverse events occurred in 15% of patients, with the most common being colitis and fatigue (1% each). Immune-mediated adverse events or infusion reactions occurred in 16% patients and were grade ≥ 3 in 6%; the most common events of any grade were colitis, hyperthyroidism, hypothyroidism, pneumonitis, and severe skin reaction. Two patients died from treatment-related adverse events, consisting of pneumonitis in one and sepsis in the other.    

The investigators concluded, “Pembrolizumab monotherapy shows antitumor activity with an acceptable safety profile in a subset of patients with RECIST-measurable and bone-predominant metastatic castration-resistant prostate cancer previously treated with docetaxel and targeted endocrine therapy. Observed responses seem to be durable, and [overall survival] estimates are encouraging.”

Johann Sebastian de Bono, MD, PhD, of The Institute of Cancer Research and Royal Marsden Hospital, London, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co. For full disclosures of the study authors, visit jco.ascopubs.org.