Immunotherapies in CRPC: Progress Evident but Not Without Challenges

Sandra Kear @skear_TargOnc
Published Online: April 24, 2014
Robert Dreicer, MD

Robert Dreicer, MD

Increasing efficacy with cancer vaccines, oncolytic viruses, and checkpoint inhibitors in clinical trials led to immunotherapy, as a whole, being deemed Breakthrough of the Year by Science magazine in 2013.1 However, for Robert Dreicer, MD, and colleagues at the Interdisciplinary Prostate Cancer Congress (IPCC) held March 2014, enthusiasm regarding these therapies for patients with castration-resistant prostate cancer (CRPC) comes with reservations.

Challenges With Sipuleucel-T

“It gets to be a challenge to use a therapy that, from a mechanistic perspective, leaves you with less insight, and that has limited some of what we have done,” said Dreicer regarding combining sipuleucel-T with various targeted therapies. Dreicer is chair of the department of solid tumor oncology at the Cleveland Clinic’s Taussig Cancer Institute and professor at the Lerner College of Medicine.

In 2010, the IMPACT trial2 showed an increase in the probability of survival with sipuleucel-T, compared with placebo, in patients with metastatic CRPC who were asymptomatic or minimally symptomatic. While the drug improved overall survival (OS) for patients with prostate cancer in the phase III trial, its use is not yet widespread, according to Dreicer. Despite the demonstrated increase in OS, sipuleucel-T is not a replacement for treatments designed to induce an objective antitumor response in real time, and it has not been shown to improve progression-free survival (PFS), according to Dreicer. He added that access and cost continue to pose problems.

Dreicer mentioned that many of his patients with prostate cancer are also reluctant to put forth the time and effort for this treatment, which is infused in 3 doses at intervals of 2 weeks, each administered after cell collection (leukapheresis or apheresis). “Men make treatment decisions much differently than women,” he said, mentioning that women are more likely to invest additional time in their own healthcare. Due to all those factors, “It is not surprising that its uptake has been a little bit challenging,” Dreicer said of sipuleucel-T.

Benefits Despite Challenges

Despite these challenges, Dreicer stands behind sipuleucel-T, stressing that the drug is part of a therapeutic paradigm in which multiple agents are used. “You layer this therapy on; it’s not an end all and be all,” he said. “Understanding that this therapy, when falling in the right place, may increase utility, is important.”

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Topline results from the phase II TERRAIN trial showed enzalutamide increased progression-free survival (PFS) by nearly 10 months compared with bicalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC).
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