Immunotherapies' Disappointing Track Record for Prostate Cancer
After a litany of failures for immunotherapies against prostate cancer, calls are mounting for approaches that combine these agents with other treatments.
Prostate cancer seems like a promising target for immunotherapy. These tumors tend to be slow-growing, and the prostate contains various tissue-specific antigens. Prostate-specific antigen (PSA) even offers a ready biomarker with which to assess early responses to investigational treatments.
Given that prostate cancer is a leading cause of cancer death among men, it is not surprising that numerous clinical trials have been undertaken to develop immunotherapy agents against it.
But instead of a growing immunotherapeutic armory, these efforts have yielded a litany of disappointments.
Oncologists hoped that targeted immune therapies like ipilimumab (Yervoy), a CTLA4 immune checkpoint inhibitor, would prove as effective against prostate tumors as they have been against melanoma. But in randomized phase 3 clinical trials, ipilimumab and other immunotherapy agents that had shown early clinical promise against prostate cancer, like sunitinib and tasquinimod (which disrupt the tumor microenvironment), failed to improve overall survival (OS), despite promising results for progression-free survival (PFS).1,2
Even the lone FDA-approved immunotherapy agent for prostate cancer, the therapeutic vaccine sipuleucel-T (Provenge), has met with “some skepticism” in the clinic, noted medical oncologist Sumanta Kumar Pal, MD, assistant clinical professor at the department of medical oncology & therapeutics research at City of Hope Cancer Center in Duarte, California.
The reasons for immunotherapies' failures against prostate cancer likely include their relatively low genetic “mutational load” compared to other cancer types like melanoma, lung cancer or bladder cancer, which are more mutation-rich, and against which immunotherapies have proven more effective, Dr Pal noted.
According to Dr Pal, disappointments like the ipilimumab monotherapy trial “may have diminished enthusiasm” for exploring other immune checkpoint blockade agents in prostate cancer, like PD-1 and PD-L1 inhibitors.
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There are 9 ongoing phase 2 and 3 clinical trials for prostate cancer vaccines, compared to 4 such trials for immune checkpoint-targeting antibodies. Monotherapy arms of phase 3 trials for tremelimumab and nivolumab were discontinued, but combination therapies are still under investigation. Four autologous cell infusion immunotherapies are undergoing phase 1 trial evaluations.