Phase 3 Trial in Prostate Cancer Subset Discontinued Due to Lack of Survival Benefit

A data monitoring committee recommended to stop the phase 3 trial in metastatic hormone-sensitive prostate cancer due to a lack of progression-free survival and overall survival with combination therapy.

The pharmaceutical company, Merck, announced that it will stop a phase 3 trial in patients with metastatic hormone-sensitive prostate cancer due to the lack of a positive effect with Keytruda (pembrolizumab) with Xtandi (enzalutamide) and androgen-deprivation therapy.

The suggestion to stop the KEYNOTE-991 trial came from the independent data monitoring committee (an unbiased group that supervises a clinical trial and its results to see if they are acceptable), according to a press release from Merck, the manufacturer of Keytruda.

In particular, the committee determined that Keytruda with Xtandi and androgen-deprivation therapy did not improve progression-free survival (the time after treatment when a patient lives with cancer without worsening) or overall survival (the time from treatment when a patient with cancer is still alive) compared with placebo, Xtandi and androgen deprivation therapy.

“There is a significant unmet need for patients with advanced prostate cancer, and the outcome of this study is an important reminder that this disease remains very difficult to treat,” said Dr. Scot Ebbinghaus, vice president of clinical research at Merck Research Laboratories, in the release. “We are grateful to the patients and investigators for their participation in this study, and we will continue to advance our clinical development program to evaluate Keytruda-based combinations and novel candidates for patients with prostate cancer.”

Hormone-sensitive prostate cancer is a disease that requires androgens (or male hormones including testosterone) to grow. Treatment with hormone therapy — androgen-deprivation therapy — can block or stop androgens, potentially reducing the speed of cancer growth.

Although patients may initially respond to androgen deprivation therapy alone, most patients progress to castration-resistant prostate cancer (when cancer grows even with reductions in testosterone) and no longer respond to the hormone therapy within three years.

Researchers conducting the KEYNOTE-991 trial enrolled 1,251 patients with metastatic hormone-sensitive prostate cancer. Patients were assigned Xtandi and androgen-deprivation therapy either with Keytruda or placebo.

In addition to progression-free survival and overall survival, other factors to be assessed included duration of response (the time from when a patient received their assigned treatment to disease progression or death in those who had a complete or partial response to the therapy), objective response rate (the percentage of patients with a partial or complete response to treatment within a given amount of time) and safety, according to the release.

In the trial, Keytruda demonstrated a consistent safety profile to that of previous studies, according to the release. Although no new side effects were observed with Keytruda, the combination of Keytruda, Xtandi and androgen deprivation therapy was linked with a higher incidence of severe, life-threatening or fatal side effects compared to the placebo group.

Findings from the KEYNOTE-991 trial up to when the trial was stopped will be presented at an upcoming medical meeting, according to the release.

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