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The addition of pembrolizumab (Keytruda) to docetaxel for patients with metastatic castration-resistant prostate cancer (mCRPC) did not improve overall or radiographic progression-free survival versus docetaxel alone in the phase III . The findings were presented at the recent Genitourinary Cancers Symposium.

In this exclusive video, lead study author , professor of medicine and urology at the Yale School of Medicine in New Haven, Connecticut, discusses the study results.

Following is a transcript of his remarks:

The role of immune therapy is being defined in castrate-resistant disease. There have been some studies that have looked at pembrolizumab as a single agent in castrate-resistant prostate cancer, and there is an FDA approval for those patients who have microsatellite instability. However, it's not known what the role of pembrolizumab is in the general population, and whether this combines well with chemotherapy.

And the thought was that you would cause cellular damage with the chemotherapy, and then immune checkpoint therapy would stimulate the immune system, and then help clean up some of the cells that have gotten apoptotic.

So the KEYNOTE-921 study was a trial that was designed to evaluate the role of pembrolizumab in the chemotherapeutic combination of docetaxel and prednisone. So it's been observed that in patients who have received a next-generation antiandrogen, such as abiraterone (Zytiga), that the survival is shorter than what you would see in a patient who was treated with docetaxel.

So there was a study that looked at docetaxel after patients who had progressed on abiraterone, and found that the median survival was about 13 months. This was lower than the 19-month median survival seen with docetaxel in some of the phase III studies. So the trial was designed based upon some data generated from a phase II trial that looked at pembrolizumab and docetaxel that showed an improvement of radiographic progression-free survival by about 6 months with the combination.

So KEYNOTE-921 was designed to evaluate that question. More than 1,000 patients randomized received either pembrolizumab plus docetaxel and prednisone versus docetaxel and prednisone alone. There were co-primary endpoints of progression-free survival and overall survival. Unfortunately, neither of those initial endpoints were met. There was a very similar survival with docetaxel/pembrolizumab compared to the control arm. Same thing with radiographic progression-free survival.

Other secondary endpoints included tumor response rate and time to next anti-cancer treatment. The objective response rate was exactly the same in both arms, and the time to next cancer treatment was exactly the same.

The toxicity profile was really consistent with the prior toxicities of both drugs. And so no additional toxicities were noted.

So in summary, the standard of care for castration-resistant prostate cancer for chemotherapy remains docetaxel. Pembrolizumab does not add. And the real question is, Why did this study fail?

We clearly need to interrogate the tissue and understand what some of the molecular markers are of the patients who perhaps did benefit from this. And of course, how can we design future trials to encompass these findings.

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