620P Pembrolizumab (pembro) plus docetaxel and prednisone in patients with abiraterone acetate (abi)- or enzalutamide (enza)–pretreated metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-365 cohort B update

Pembro + docetaxel and prednisone (cohort B) has shown antitumor activity in patients (pts) with mCRPC in the phase I/II KEYNOTE-365 study (NCT02861573). Updated results from cohort B, including time to symptomatic skeletal event, radiographic bone progression, and radiographic soft tissue progression, are reported. Pts who received abi or enza for ≤4 wk in the prechemotherapy mCRPC setting and whose disease progressed within 6 mo of screening were eligible. Pts received pembro 200 mg IV + docetaxel 75 mg/m2 IV Q3W and prednisone 5 mg orally twice daily. Primary end points: PSA response rate (decrease ≥50% from baseline), ORR per RECIST v1.1 by blinded independent central review, and safety. Secondary end points: DCR, DOR, rPFS per PCWG-modified RECIST, OS, time to symptomatic skeletal event, radiographic bone progression, and radiographic soft tissue progression. 104 of 105 enrolled pts were treated; 50% had measurable disease. Median (range) time from enrollment to data cutoff was 19.9 (1.4-27.8) mo for all pts and 21.8 (17.9-27.8) mo for pts with ≥27 wk follow-up (n = 72). Confirmed PSA response rate was 28% in 103 pts with baseline PSA assessment. In pts with measurable disease and ≥27 wk follow-up (n = 39), confirmed ORR was 18% (7/39, all PR). For all pts, median rPFS was 8.3 mo (95% CI, 7.6-10.1) and median OS was 20.4 mo (95% CI, 16.9-NR). At 12 mo, rPFS rate was 24.0% and OS rate was 75.8% by Kaplan-Meier. Additional efficacy analyses are displayed in the table. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 40% of pts; 2 pts died of TRAEs (pneumonitis). Pembro + docetaxel and prednisone continued to show antitumor activity and acceptable safety in pts with abi- or enza-pretreated mCRPC. KEYNOTE-921 phase III study of this combination is ongoing (NCT03834506).Table: 620MODCR, n/N (%)aMeasurable disease20/39 (51)Nonmeasurable disease17/33 (52)Total37/72 (51)DOR, median (range), moa6.7 (3.4-9.0+)bResponse ≥6 mo, n/N (%)5/7 (71)Median, mo (95% CI)Time to confirmed PSA progression6.2 (3.7-7.4)Time to symptomatic skeletal-related event25.9 (18.3-NR)Event-free survival rate at 12 mo, %73.1Time to radiographic bone progression10.3 (9.0-12.2)Event-free survival rate at 12 mo, %36.7Time to radiographic soft tissue progression12.4 (9.7-NR)Event-free survival rate at 12 mo, %54.9aWith ≥27-wk potential follow-up; b ‘+’ indicates ongoing responder; NR, not reached. Open table in a new tab