Keynote-365 cohort a: Pembrolizumab (pembro) plus olaparib in docetaxel-pretreated patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC).

Abstract

145 Background: Activity with pembro or olaparib has been observed in mCRPC pts who progressed on 2nd-generation hormonal therapy (HT) and chemotherapy. From KEYNOTE-365 (NCT02861573), a phase 1b/2 umbrella study testing combinations in mCRPC, we report early results from cohort A combining pembro + olaparib. Methods: Pts with mCRPC were eligible if they progressed within 6 months prior to screening determined by either PSA progression or radiologic progression in bone or soft tissue. Pts were docetaxel-pretreated for mCRPC, may have received 1 other chemotherapy, and had ≤2 2nd-generation HT. Pts received pembro 200 mg IV Q3W + olaparib 400 mg orally twice daily. Primary end points: safety and PSA response rate (confirmed PSA decline ≥50%). Key secondary end points: ORR RECIST v1.1 (investigator review), disease control rate (DCR: CR+PR+SD ≥6 mo), time to PSA progression, composite response rate (ORR RECIST v1.1, confirmed PSA response, or confirmed decrease in circulating tumor cell count from ≥5 to <5 cells/7.5 mL blood), rPFS, and OS. Results: Median follow-up was 11 mo. 41 initiated treatment (median age 69 years; PD-L1+ 27%; visceral disease 42%; RECIST-measurable 68%; homologous recombination repair mutation [HRR] 0%). See efficacy in table below. Treatment-related AEs occurred in 39 (95%) pts. Most frequent (≥30%) were anemia (37%), fatigue (34%), and nausea (34%). Grade 3-5 treatment-related AEs were in 21 (51%) pts. There were 2 deaths; only 1 was treatment-related (cause unknown). Conclusions: Combination of pembro + olaparib has activity in pts previously treated with docetaxel and ≤2 2nd-generation HT for mCRPC and who are HRR wild type. Observed safety profile for the combination is consistent with individual profiles of pembro and olaparib. Clinical trial information: NCT02861573. [Table: see text]

PARP Inhibitors in Prostate and Urothelial Cancers

“…Cohort A of the phase Ib Keynote-365 clinical trial is evaluating the safety and antitumor activity of the combination of pembrolizumab (200 mg IV every 3 weeks) along with olaparib (400 mg orally twice daily). Preliminary results were presented at ASCO Genitourinary symposium in 2019 (36). In 41 patients with metastatic CRPC previously treated with chemotherapy and novel hormonal agent, the combination therapy had a median PFS per prostate cancer working group 3 (PCWG-3) RECIST criteria of 5 months and a median OS of 14 months.…”

Previous, Current, and Future Pharmacotherapy and Diagnosis of Prostate Cancer—A Comprehensive Review

“…Inhibition of PD-L1 may be a new key for cancer treatment. The results of combined therapy of pembrolizumab and olaparib, presented by Evan Yu in 2019 at Genitourinary Cancers Symposium in San Francisco are promising [106].…”

ARAMIS: Efficacy and safety of darolutamide in nonmetastatic castration-resistant prostate cancer (nmCRPC).

“…tate Cancer), evaluated darolutamide in the metastatic CRPC setting. [9][10][11] In these trials, darolutamide was associated with PSA decreases of 50% or more in 65% to 83% of patients, and an overall response rate (ORR) of 30%. No clear drug-related side effects were reported.…”

“…Dr Evan Yu provided data for cohort A of the KEYNOTE-365 trial (Phase Ib/II Trial of Pembrolizumab [MK-3475] Combination Therapies in Metastatic Castration-Resistant Prostate Cancer [mCRPC]). 11 Patients in this cohort had metastatic CRPC previously treated with docetaxel. They were not selected based on genetic analysis.…”