The phase 3 KEYLYNK-010 trial exploring the immunotherapy pembrolizumab (Keytruda) in combination with the PARP inhibitor olaparib (Lynparza) in heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) has been discontinued for futility, according to Merck (MSD), the developer of pembrolizumab and a codeveloper of olaparib.1
The KEYLYNK-010 trial (NCT03834519) compared the pembrolizumab/olaparib combination with abiraterone acetate (Zytiga) or enzalutamide (Xtandi) in patients with mCRPC who had progressed on prior chemotherapy and either abiraterone acetate or enzalutamide. An independent Data Monitoring Committee recommended discontinuing the study after a planned interim analysis showed that pembrolizumab/olaparib did not improved overall survival (OS) versus either abiraterone or enzalutamide. An earlier interim analysis had shown that the immunotherapy/PARP inhibitor combination also did not improve radiographic progression-free survival (rPFS) versus the control arm.
“There remains a significant unmet need for patients diagnosed with advanced prostate cancer, who have a poor prognosis after not responding to initial therapy,” Roy Baynes, MD, PhD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, stated in a news release. “Merck continues to evaluate the combination of Keytruda and Lynparza in a range of cancers, and to research other Keytruda-based combinations for patients with advanced prostate cancer. We are grateful to the patients, their families and the investigators who made this study possible.”
Overall, the open-label KEYLYNK-010 trial included 793 patients unselected for homologous recombination repair defects. The dual primary end points of the trial were OS and rPFS. There were no new safety signals with the pembrolizumab/olaparib combination compared with prior studies for the individual treatments; of note, however, there was a higher incidence of grade 3-5 adverse events with the experimental combination versus the control group.
Merck and AstraZeneca, the other co-developer of olaparib, are also collaborating on the phase 3 PROpel trial, which has had greater success. Results from the placebo-controlled trial presented during the 2022 ASCO Genitourinary Cancers Symposium showed that adding olaparib to frontline abiraterone significantly improved rPFS in patients with mCRPC.2
The median investigator-assessed rPFS was 24.8 months with olaparib/abiraterone vs 16.6 months with placebo/abiraterone, translating to a 34% reduction in the risk of radiographic disease progression or death (HR, 0.66; P <.0001). When evaluated by blinded independent central review, the median rPFS with olaparib/abiraterone was 27.6 months vs 16.4 months with placebo/abiraterone, translating to a 39% reduction in the risk of radiographic disease progression or death (HR, 0.61; P <.0001).
OS data, which at the time of the presentation were at 28.6% maturity, showed that the median OS was not reached in either arm but trended toward improved survival with olaparib/abiraterone vs placebo/abiraterone (HR, 0.86; prespecified 2-sided alpha P = .29).
1. Merck Announces KEYLYNK-010 Trial Evaluating KEYTRUDA® (pembrolizumab) in Combination with LYNPARZA® (olaparib) in Patients with Metastatic Castration-Resistant Prostate Cancer to Stop for Futility. Published online March 15, 2022. Accessed March 15, 2022. https://bit.ly/37ClsI5
2. Saad F, Armstrong AJ, Thiery-Vuillemin A, et al. PROpel: phase III trial of olaparib (ola) and abiraterone (abi) versus placebo (pbo) and abi as first-line (1L) therapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2022;40(suppl 6):11. doi:10.1200/JCO.2022.40.6_suppl.011 doi:10.1200/JCO.2022.40.6_suppl.011