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Response and survival rates with the immunotherapy-based regimen support ongoing phase 3 research with pembrolizumab in prostate cancer.
The triplet of pembrolizumab (Keytruda), docetaxel, and prednisone continued to demonstrate promising activity in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed on abiraterone acetate (Zytiga) or enzalutamide (Xtandi).
Updated cohort findings from the 1b/2 KEYNOTE-365 trial presented during the 2020 European Association of Urology Virtual Congress showed that the pembrolizumab-based regimen induced a confirmed PSA response of 28.2% in the overall cohort population, with 70.9% of patients experiencing a PSA decrease from baseline.1 Among patients with RECIST-measurable disease who had ≥27 weeks’ follow-up, the objective response rate (ORR) was 17.9% (all partial responses) and the disease control rate was 51.3%.
Among all patients in the cohort, the median radiographic progression-free survival (rPFS) was 8.3 months and the median overall survival (OS) was 20.4 months. The 6-month rPFS rate was 72.8% and the 6-month OS rate was 95.3%.
“With increased enrollment and additional follow-up, pembrolizumab plus docetaxel and prednisone continued to show promising activity in patients previously treated with abiraterone or enzalutamide in the prechemotherapy state for mCRPC,” said lead author Gwenaelle Gravis, MD, of the Institut Paoli-Calmettes, Marseille, France.
The KEYNOTE-365 trial evaluated several combinations of pembrolizumab and other agents in patients with mCRPC. In cohort B, patients received pembrolizumab plus docetaxel and prednisone. Patients had prior treatment with enzalutamide or abiraterone, but not both. Patients were also required to have progressive disease ≤6 months before screening.
Overall, 104 patients were enrolled in cohort B. The median age was 68 years (range, 50-86) and 24% were PD-L1 positive. Half of patients had measurable disease and one-fourth of patients had visceral disease. The median follow-up for the overall cohort population was 13 months.
Of the total cohort population, 72 patients had ≥27 weeks of potential follow-up, including 39 with RECIST measurable disease, and 33 with RECIST nonmeasurable disease. The median duration of follow-up was 19 months for these patients. Among the 39 patients with measurable disease, there were 7 partial responses and 22 patients had stable disease. The median duration of response was 6.7 months.
Overall, half of the 104 patients discontinued, mainly due to disease progression (55%).
Safety was evaluated in all 104 patients, with 96% of patients experiencing at least 1 treatment-related adverse event (TRAE) of any grade. The most common TRAEs across all grades were alopecia (39.4%), diarrhea (38.5%), fatigue (38.5%), dysgeusia (25%), nausea (24%), peripheral neuropathy (20.2%), asthenia (17.3%), anemia (15.4%), decreased appetite (13.5%), mucosal infection (12.5%), febrile neutropenia (11.5%), and peripheral edema (10.6%).
Grade 3 to 5 TRAEs occurred in 40.4% of patients. The most frequently occurring grade 3 to 5 TRAEs were febrile neutropenia (11.5%), anemia (4.8%), diarrhea (2.9%), fatigue (1.9%), asthenia (1%), and peripheral edema (1%). There were 2 deaths related to an AE (pneumonitis) that the investigators considered to be treatment related.
The combination of pembrolizumab plus docetaxel and prednisone is being explored in the ongoing phase 3 KEYNOTE-921 trial (NCT03834506).2 The double-blind study is accruing chemotherapy-naïve patients with mCRPC and prior abiraterone and enzalutamide and randomizing them to the pembrolizumab combination or placebo plus docetaxel and prednisone.
The coprimary end points are OS and rPFS. The target enrollment for the trial is 1000 patients and the study is being conducted at nearly 200 locations across the world. The estimated primary completion date is September 12, 2021.
1. Gravis G, Kolinsky M, Mourey L, et al. KEYNOTE-365 cohort B updated results: Pembrolizumab (pembro) plus docetaxel and prednisone in abiraterone (abi) or enzalutamide (enza)-pretreated patients with metastatic castration-resistant prostate cancer (mCRPC). 2020 European Association of Urology Virtual Congress. July 17-26, 2020. Abstract 560.
2. NIH US National Library of Medicine: ClinicalTrials.gov. Study of Pembrolizumab (MK-3475) Plus Docetaxel Versus Placebo Plus Docetaxel in Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-3475-921/KEYNOTE-921). Posted February 8, 2019. https://bit.ly/31Ppkik. Accessed August 14, 2020.