Pembrolizumab plus docetaxel failed to elicit a statistically significant improvement in overall survival and radiographic progression-free survival in patients with metastatic castration-resistant prostate cancer, missing the coprimary end points of the phase 3 KEYNOTE-921 trial.
Pembrolizumab (Keytruda) plus docetaxel failed to elicit a statistically significant improvement in overall survival (OS) and radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer (mCRPC), missing the coprimary end points of the phase 3 KEYNOTE-921 trial (NCT03834506).1
The combination induced numerical improvements vs docetaxel alone, but those did not reach statistical significance. The results also indicated that the safety profile of pembrolizumab was consistent with that reported in prior trials. Investigators plan to present full data at an upcoming medical meeting.
“Results from this study serve as an important reminder that metastatic prostate cancer remains very difficult to treat, and more research is needed. We will continue to advance our clinical development program to evaluate pembrolizumab-based combinations and novel candidates for patients with this disease,” Eliav Barr, MD, senior vice president, head of global clinical development and chief medical officer of Merck Research Laboratories, said in a press release. “We are grateful to the patients and investigators for their participation in this study.”
KEYNOTE-921 is a randomized, double-blind phase 3 trial evaluating pembrolizumab in combination with docetaxel and prednisone compared with placebo plus chemotherapy and prednisone.2 The study enrolled patients with mCRPC who had not received chemotherapy for mCRPC but whose disease had progressed on or was intolerant to a next-generation hormonal agent.
Additional eligibility criteria stated that patients have ongoing androgen deprivation with serum testosterone level below 50 ng/dL, provide a newly obtained core or excisional biopsy from soft tissue not previously irradiated or bone biopsy in the case of bone only or bone predominant disease, and an ECOG performance status of 0 or 1.
Moreover, patients receiving bone resorptive therapy including, but not limited to, bisphosphonate or denosumab must have been on stable doses prior to randomization.
The trial enrolled 1030 patients who were subsequently randomly assigned to 200 mg of pembrolizumab every 3 weeks for up to approximately 2 years plus 75 mg/m2 of docetaxel and 5 mg of prednisone twice daily for approximately 7 months. Patients in the control arm were assigned to placebo plus docetaxel and prednisone on the same schedule.
Notably, on day 1 of each 3-week cycle, patients received 8 mg of oral dexamethasone at 12 hours, 3 hours, and 1 hour prior to docetaxel administration.
OS and rPFS are the coprimary end points of the study. Secondary end points include time to initiation of the first subsequent anti-cancer therapy, prostate-specific antigen response rate, objective response rate, and duration of response.
The company stated that studies evaluating pembrolizumab as monotherapy and in combination with other anti-cancer therapies in prostate cancer including in the phase 2 KEYNOTE-199 (NCT02787005) and KEYNOTE-365 (NCT02861573) trials, and the phase 3 registrational KEYNOTE-641 (NCT03834493) and KEYNOTE-991 (NCT04191096) trials.