Evan Yu, MD, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington, reviews results from the phase 3 KEYLYNK-010 study, evaluating pembrolizumab plus olaparib for patients with heavily pretreated metastatic castration-resistant prostate cancer. In this randomized, open label trial, pembrolizumab plus olaparib did not improve the radiographic progression-free survival or overall survival when compared to abiraterone or enzalutamide.

Dr Yu addresses some of the subgroups of interest in this trial, including patients with BRCA mutations and those in North America.

These results were first presented at the 2022 European Society for Medical Oncology Congress in Paris, France.

Transcript:

Hello, my name's Evan Yu and I'm a professor at the Fred Hutchinson Cancer Center, University of Washington in Seattle, Washington. Today I'm going to discuss my presentation at ESMO, which was the KEYLYNK-010 Randomized Open Label Phase 3 Trial. This trial randomized patients with metastatic castration-resistant prostate cancer to pembrolizumab plus olaparib versus either abiraterone or enzalutamide, for patients who were previously treated and who were molecularly unselected.

This trial enrolled around 800 patients with metastatic castration-resistant prostate cancer who had progressive disease after either abiraterone or enzalutamide, but not both. Also, they needed to have progressive disease after docetaxel. They were randomized, 2-to-1, two in favor of pembrolizumab plus olaparib, and one in favor of abiraterone or enzalutamide. If the patient had received previous enzalutamide, they were randomized to abiraterone. If they had received abiraterone, they would then receive enzalutamide.

The trial had dual primary endpoints of radiographic progression-free survival and overall survival. The trial accrued a heavily pretreated population with ECOG performance status of 1 in around 50% of patients. It was a fairly even split, between prior abiraterone or prior enzalutamide, and we saw about a quarter of the patients that were homologous recombination repaired gene altered. This is consistent with other reports in the field for this patient population. Similarly, BRCA-altered patients were slightly less than 10%, and that is also similar to what one might expect in this field.

The primary endpoint of radiographic for progression-free survival was not met by pembrolizumab plus olaparib and the hazard ratio was 1.02 compared to the other novel hormonal therapy agent arm. Subgroups that were of interest, however, were the BRCA-mutated population, where we saw the forest plot fall far to the left of the 1, and the confidence interval did not cross, and that's to be expected for BRCA-mutated patients that are receiving a PARP inhibitor.

The other dual primary end point was overall survival, and in the intention-to-treat population, we saw a median of 15.8 months for pembrolizumab plus olaparib, 14.6 months for novel hormonal therapy agent, and this hazard ratio was 0.94 in favor of pembrolizumab plus olaparib, but was not statistically significant with a P value of 0.26. Subgroups of interest, again, BRCA-mutated population as one might expect, and interestingly, the small North American population also seemed to do well in favor of pembrolizumab plus olaparib.

Otherwise, one secondary end point that did seem in favor of pembrolizumab plus olaparib was the patient population that had soft tissue disease and looking at objective response rate, which was 16.8% for pembrolizumab plus olaparib, 5.9% for novel hormonal therapy agent, and the confidence intervals did not cross.

In regards to safety, we saw what we might expect in this study. We did see more grade ≥3 or adverse events for pembrolizumab plus olaparib at 34.6% vs 9% for novel hormonal therapy agent, and this is as expected. Additionally, we saw more treatment-related adverse events overall, and we saw things that one might expect from pembrolizumab plus olaparib. Anemia, gastrointestinal side effects, rash, those were the most common treatment-related adverse events.

In conclusion, the randomized phase 3 KEYLYNK-010 trial did not show statistically significant improvement in progression-free survival or overall survival of pembrolizumab plus olaparib versus the active comparator of novel hormonal therapy agent, for a patient population with metastatic castration resistant prostate cancer, that was previously treated and molecularly unselected. The study was stopped early by the external data monitoring committee at the prespecified interim analysis. Objective response rate, however, was higher for pembrolizumab plus olaparib versus the novel hormonal agent group and adverse events were generally as expected. Thank you very much.

Source:

Yu EY, Goh JCH, Shin SJ, et al. “1362MO – Pembrolizumab + olaparib vs abiraterone (abi) or enzalutamide (enza) for patients (pts) with previously treated metastatic castration-resistant prostate cancer (mCRPC): Randomized open-label phase III KEYLYNK-010 study.” Presented at European Society for Medical Oncology Congress; September 9-13, 2022