Recently Approved Therapies Bring New Understanding in Management of Prostate Cancer

Bryan A. Mehlhaff, MD

After many years of treating patients with advanced prostate cancer the same way, a host of new drug approvals has not only changed the way urologists manage prostate cancer but their understanding of the disease as well.

“It’s been an exciting time to be a urologist treating prostate cancer,” said Bryan A. Mehlhaff, MD, principal investigator in the division of clinical research at the Oregon Urology Institute and a member of the Board of Directors of the Large Urology Group Practice Association (LUGPA).

At this year’s annual LUGPA meeting, held in Chicago November 1-3, Mehlhaff gave a presentation on the use of sipuleucel-T (Provenge), an autologous cellular immunotherapy approved by the FDA in 2010 to treat patients with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). In addition to extending survival, Mehlhaff said that he has found it easier to communicate the benefits of sipuleucel-T with his patients.

“Rather than say that I’m going to give a cytotoxic therapy or some other drug to treat the prostate cancer, I’m able to say that I can take that patient’s own cells and help the body’s own immune system fight the prostate cancer,” Mehlhaff said. “It plays much better to the patient.”

Mehlhaff noted that all of these approved therapies showed roughly the same survival benefit in the clinical trials that served as the basis for their respective approvals. Sipuleucel-T showed an improvement in overall survival (OS) of 4.1 months, abiraterone acetate (Zytiga) demonstrated a 4.6 month improvement in OS, and enzalutamide (Xtandi) showed a 4.8 month OS improvement.

“We hold prostate cancer to a very stringent level of proof that these therapies actually help the patients,” Mehlhaff said. “So we have to figure out how to properly sequence these new drugs so that the benefits of each individual drug are able to accumulate.”

Sequencing does matter, since both abiraterone acetate and enzalutamide are currently approved only for patients who have been previously treated with a chemotherapy regimen containing docetaxel, whereas sipuleucel-T is given in the front-line setting. Since chemotherapy can weaken the immune system, Mehlhaff said that he would not advise any patient to receive chemotherapy prior to sipuleucel-T, and that abiraterone and enzalutamide would likely come after sipuleucel-T if a patient relapses.

Mehlhaff said urologists are eagerly awaiting further results of clinical trials of abiraterone acetate as a front-line therapy. If those results are positive, he added that moving abiraterone acetate into an earlier setting could significantly expand the sequencing options urologists have. Mehlhaff said it is crucial for large urology practices to keep up to date on the constant flow of information regarding new drugs and how they can be applied clinically.

“It’s usually up to at least one or two physicians in a practice to stay on top of this information and communicate with everyone else in the group to make sure we’re all on the same page,” Mehlhaff said.

The other major development in the treatment of prostate cancer has been the advent of bone-targeted therapies. Currently, denosumab (Xgeva) is approved to treat patients with mCRPC whose cancer has metastasized to the bone, something that happens in approximately 90% of advanced prostate cancer cases. Mehlhaff said that the first study looking at bone metastases was published about 15 years ago. Since then, urologists have come to understand that monitoring bone health is an essential part of managing patients with prostate cancer.

Mehlhaff said that his practice uses physicians’ assistants (PAs) to make sure patients follow-up with bone health practices. While some large urology groups have begun handling bone health matters within the clinic by performing dual-energy x-ray absorptiometry (DXA) scans on-site, clinics that do not have those on-site resources can have their PAs follow up with patients to make sure they receive all of the appropriate tests.

“It’s been a huge educational process,” Mehlhaff said. “But it’s something that we and many other clinics have been able to handle much better in recent years because of the steps we’ve taken.”