medwireNews: Pembrolizumab monotherapy shows activity against both RECIST-measurable and bone-predominant treatment-refractory metastatic castration-resistant prostate cancer (mCRPC), results of the KEYNOTE-199 phase 2 trial show.
Furthermore “[o]bserved OS [overall survival] estimates are promising, suggesting that immunotherapy may be able to extend the tail of the survival curve in a historically difficult-to-treat population,” write Johann de Bono (The Institute of Cancer Research, London, UK) and co-investigators in the Journal of Clinical Oncology.
The current analysis included data for three cohorts who were treated with intravenous pembrolizumab 200 mg every 3 weeks for up to 35 cycles. Cohort 1 consisted of 133 patients with RECIST-measurable PD-L1-positive disease, cohort 2 included 66 patients with PD-L1-negative disease, and cohort 3 included 59 patients with bone-predominant disease, regardless of PD-L1 expression.
All the patients had previously received docetaxel and one or more targeted therapies, with approximately 25% having received both enzalutamide and abiraterone.
The primary outcome of objective response rate (ORR) according to RECIST v1.1 criteria was achieved by 5% of cohort 1 and 3% of cohort 2.
The researchers note that although the ORR was “modest […], those responses that did occur were durable.” In cohort 1 the median response duration was unreached while in cohort 2 it was 10.6 months.
Among the responders, two patients in cohort 1 achieved a complete radiographic response, with the remaining five responses in cohort 1 and both responses in cohort 2 being partial responses.
A further six patients in cohort 1 and four in cohort 2 experienced stable disease for at least 6 months, resulting in disease control rates (DCRs) of 10% and 9%, respectively. In cohort 3, the DCR was 22%.
However, when de Bono and team analyzed the data according to the Prostate Cancer Working Group 3 (PCWG3)-modified RECIST criteria, the DCRs were 13%, 18%, and 39%, respectively.
“These findings highlight the importance of accurately evaluating progression in bone metastases and suggest that PCWG3-modified RECIST may be preferable for assessing antitumor activity in mCRPC,” they remark.
Median OS was 9.5, 7.9, and 14.1 months in cohorts 1, 2, and 3, respectively, with corresponding estimated 12-month survival rates of 41%, 35%, and 62%.
The majority (60%) of patients experienced at least one treatment-related adverse event (AE), typically fatigue, diarrhea, and decreased appetite. The rate of grade 3 to 5 AEs was 15% and 5% of patients discontinued treatment due to AEs. There were two deaths, due to sepsis and pneumonitis, that were considered to be treatment related by the investigators.
De Bono et al say their study shows “a clear signal of antitumor activity for pembrolizumab monotherapy in a small number of patients with previously treated mCRPC, which highlights the importance of identifying predictive biomarkers.”
They acknowledge that “[b]iomarker analyses were limited by the low number of responses and the availability of whole-exome sequencing results from only a fraction of the population.” But the team adds that “future biomarker studies from KEYNOTE-199, including exploration of different [combined positive score] cut points, gene expression profiles, and tumor mutational burden, will aim to uncover molecular markers of response to single-agent pembrolizumab.”
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