Updated KEYNOTE-365 data on metastatic castration-resistant prostate cancer are presented at ASCO GU 2021
Previous results from cohort B of the KEYNOTE-365 trial, after a median of 20 months of follow-up, demonstrated that pembrolizumab + docetaxel and prednisone were well tolerated and had antitumor activity in patients with mCRPC previously treated with abiraterone or enzalutamide
During the 2021 Genitourinary Cancers Symposium, new efficacy and safety data were presented for KEYNOTE-365 (NCT02861573), (NCT02861573), a phase Ib/II trial that evaluated pembrolizumab in combination with four different drugs (cohorts A, B, C, D) in patients with metastatic castration-resistant prostate cancer (mCRPC).
The researchers presented data from one year of additional follow-up of cohort B, regarding the analysis of the evolution of patients who did not respond or were intolerant to ≥ 4 weeks of abiraterone or enzalutamide, in the state of pre-chemotherapy mCRPC, whose disease had progressed by six months of screening (determined by increased PSA or radiological progression in bones/soft tissues). Patients received 200 mg of pembrolizumab every three weeks, docetaxel 75 mg/m² every three weeks and oral prednisone 5 mg 2x/day. The primary outcomes were security, PSA response rate (PSA decrease > 50% baseline), and objective response rate (ORR) by RECISTv1.1, through blind independent central review. Efficacy and safety were evaluated in all treated subjects.
Results:
Of the 104 treated patients, the mean age was 68.0 years; 23.1% had tumors with the positive expression for PD-L1(combined positive score [CPS] ≥ 1); 25.0% had visceral disease and 50.0% had measurable disease. The average time from registration to cutoff date was 32.4 months. 101 patients discontinued treatment, mainly due to disease progression (77.9%).
Efficacy results of keynote-365 cohort B
| PSA n/N response rate (%) | 35/103 (34) |
| ORR, measurable disease, n/N (%) | 12/52 (23,1); 12 partial responses |
| Disease control rate | |
| Measurable disease | 38/52 (73,1) |
| Non-measurable disease | 41/52 (78,8) |
| Total | 79/104 (76,0) |
| Median response duration (months) | 6,3 (3,4-9,0) |
| Response ≥6 months, n (%) | 8 (66,7) |
| Median (95% CI) | |
| Time to PSA progression, weeks | 29,3 (21,1-32,1) |
| Radiological PFS, months | 8,5 (8,3-10,1) |
| Overall survival, months | 20,2 (16,9-24,2) |
Treatment-related adverse events (TRAEs) occurred in 100 men (96.2%). The most frequent (≥30%) were: diarrhea (41.3%), fatigue (41.3%) and alopecia (40.4%). Grade 3-5 TRAEs occurred in 46 patients (44.2%). Five (4.8%) died due to adverse events, and two pneumonitis were related to treatment.
Therefore, after another year of follow-up, pembrolizumab + docetaxel and prednisone showed better objective and PSA response rates compared to the previous data set in patients with mCRPC previously treated with abiraterone or enzalutamide. Safety was consistent with the known profiles of each agent and will be assessed later in a phase III trial (KEYNOTE-921).
References:
Appleman LJ, et al. KEYNOTE-365 cohort B: Pembrolizumab (pembro) plus docetaxel and prednisone in abiraterone (abi) or enzalutamide (enza)–pretreated patients with metastatic castration-resistant prostate cancer (mCRPC)—New date after an additional 1 year of follow-up. Abstract 10. 2021 Genitourinary Cancers Symposium. DOI:10.1200/JCO.2021.39.6_suppl.10.
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