Despite Improving Responses, Pembrolizumab/Olaparib Fails to Improve Survival in mCRPC

Pembrolizumab (Keytruda) plus olaparib (Lynparza) did not yield an improvement in survival despite higher responses vs novel hormonal agents (NHA) such as abiraterone (Zytiga) or enzalutamide (Xtandi) in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC), according to data from the phase 3 KEYLYNK-010 study (NCT03834519).

Median radiographic progression-free survival (rPFS) in the pembrolizumab/olaparib arm was 4.4 months (95% CI, 4.2-6.0) vs 4.2 months (95% CI, 4.0-6.1) with NHA (HR 1.02; 95% CI, 0.82–1.25; P = .55) at the first interim analysis. Moreover, median OS was 15.8 months (95% CI, 14.6-17.0) with pembrolizumab plus olaparib vs 14.6 months (95% CI, 12.6-17.3) in the control arm (HR 0.94; 95% CI, 0.77–1.14; P = .26) at the second interim analysis.

The ORR in the experimental arm was 16.8% (95% CI, 12.3%-22.1%) vs 5.9% (95% CI, 2.4%-11.7%) in the control arm. The disease control rate in each respective arm was 32.4% (95% CI, 26.5%-38.6%) compared with 19.3% (95% CI, 12.7%-27.6%). Additionally, the complete response (CR) and partial response (PRs) rates were 1.6% and 15.2%, respectively, in the combination arm compared with no CRs and a PR rate of 5.9% in the control arm.

The study evaluated 793 patients who were randomly assigned 2:1 to receive either pembrolizumab at 200 mg every 3 weeks for 35 cycles or less plus 300 mg of olaparib, or 1000 mg of abiraterone in those previously treated with enzalutamide or 160 mg of enzalutamide in those previously treated with abiraterone. To be eligible, patients were required to have histologically or cytologically confirmed mCRPC and have experienced disease progression following prior treatment with either abiraterone or enzalutamide.

The average patient age was 71 years (range, 40-89) in the experimental arm vs 69 years (range, 49-84) in the control arm. In the experimental arm and control arm, respectively, approximately half of patients (51.4% vs 47.3%) had an ECOG performance status of 1. Most patients had non­–homologous recombination repair-mutated disease in both the experimental and control arms, respectively (67.1% vs 65.5%). Moreover, most patients in both respective arms had non­–BRCA-mutated disease (83.4% vs 78.8%). Over half of patients in both the pembrolizumab and NHA arms, respectively, underwent prior treatment with abiraterone (54.6% and 54.2%) and fewer were treated with enzalutamide (45.4% vs 45.5%). Nearly all patients in both arms underwent prior treatment with docetaxel (99.2% vs 99.2%).

In terms of other findings, the median time to first subsequent therapy (TFST) was 7.2 months (95% CI, 6.7-8.1) in the experimental arm and 5.7 months (95% CI, 5.0-7.1) in the control arm (HR 0.86; 95% CI, 0.71–1.03) at the first interim analysis.

Treatment-related adverse effects (TRAEs) occurred in 88.2% of patients in the experimental arm and 50.8% of patients in the control arm. Common TRAEs in the experimental arm and control arms, respectively, were anemia (46% vs 2.7%), nausea (35.6% vs 5.1%), fatigue (25.7% vs 16.4%), decreased appetite (21.3% vs 4.7%), and asthenia (13.5% vs 7.0%).

Reference

Yu EY, Park SH, Goh JCH, et al. Pembrolizumab plus olaparib vs abiraterone or enzalutamide for patients with previously treated metastatic castration-resistant prostate cancer: randomized open-label phase 3 KEYLYNK-010 study. Ann Oncol. 2022;33(suppl 7):1362MO. doi:10.1016/annonc/annonc1070