Pembrolizumab and Chemotherapy Does Not Meet Primary End Points Despite Modest OS, rPFS Improvement in mCRPC

Results from the phase 3 KEYNOTE-921 trial showed the primary end points of overall survival and radiographic progression-free survival were not met despite a trend towards improvement following treatment with pembrolizumab and docetaxel in patients with metastatic castration-resistant prostate cancer.

Although investigators reported a trend towards modest improvements, the primary end points of overall survival and radiographic progression-free survival were not met in the phase 3 KEYNOTE-921 trial (NCT03834506), analyzing pembrolizumab (Keytruda) plus docetaxel vs chemotherapy alone for patients with metastatic castration-resistant prostate cancer (mCRPC), according to a press release from Merck.

Investigators noted that the slight improvements in patients who were treated with pembrolizumab and chemotherapy did not meet statistical significance per the prespecified analysis. Additionally, the regimen’s safety profile remained consistent with previously reported findings. Full results will be presented at an upcoming 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 at Merck Research Laboratories, said in the press release. “We are grateful to the patients and investigators for their participation in this study.”

A total of 1030 patients were included in the randomized, double-blind trial. Patients received either 200 mg of pembrolizumab every 3 weeks for up to 2 years plus 75 mg/m2 of docetaxel up to 10 cycles and 5 mg of prednisone or placebo plus the same chemotherapy and prednisone backbone. Secondary end points included initiation of first subsequent anti-cancer therapy, prostate-specific antigen response rate, objective response rate, and duration of response.

Patients were eligible for treatment if they had histologically or cytologically confirmed adenocarcinoma without small cell histology, disease progression while receiving androgen deprivation therapy (ADT) within 6 months of screening, or current evidence of metastatic disease such as bone lesions identified by bone scans and/or soft tissue disease identified by computed tomography or magnetic resonance imaging. Additionally, patients had to have received prior treatment with 1 next-generational hormonal agent for mCRPC or metastatic hormone-sensitive prostate cancer and have progressed on treatment or became intolerant to the drug. Moreover, patients need to be receiving ongoing ADT with serum testosterone of less than 50 ng/dL. Additionally, bone resorptive therapy with stable doses prior to randomization was required.

Exclusion criteria included having a known malignancy that is progressing or requiring active treatments within the last 3 years, an autoimmune disease requiring systemic treatment within the last 2 years, or having undergone a major surgery such as local prostate intervention within 28 days prior to randomization and not having recovered from the toxicities or complications. Patients were also excluded from the trial if they had a gastrointestinal disorder that affects absorption or hinders the ability to swallow tablets, an active infection requiring systemic therapy, or a history of pneumonitis that required steroids or active pneumonitis.


Merck provides update on phase 3 KEYNOTE-921 trial evaluating Keytruda (pembrolizumab) plus chemotherapy in patients with metastatic castration-resistant prostate cancer. News Release. Merck. August 3, 2022. Accessed August 4, 2022.