PCa immunotherapy: Response better when given before ADT

Administering sipuleucel-T (Provenge) before androgen deprivation therapy in men with hormone-sensitive biochemically recurrent prostate cancer appears to result in a more robust immunologic response than when the immunotherapy is given after androgen deprivation therapy, according to a new phase II randomized trial.

“Patients who failed radical prostatectomy and/or radiation therapy were selected for this trial, whereby they had PSA relapse and were considered at high risk for progression. This patient population still represents an unmet need regrading an approved therapy, as these patients invariably receive a form of androgen deprivation therapy, with its attendant well-described adverse events,” said study co-author Neal D. Shore, MD, of Carolina Urologic Research Center, Myrtle Beach, SC. “Sequencing sipuleucel-T either before or after androgen deprivation therapy was well tolerated, and there was a suggestion that the immunologic parameters evaluated were more robust when sip-T was given before ADT. Nonetheless, additional and larger patient cohorts are needed to confirm these findings.”

The ideal would be to have an immune-oncologic therapy that could preclude or delay androgen deprivation therapy use in prostate cancer, Dr. Shore told Urology Times.

“[This] would be a welcome addition to the prostate cancer armamentarium and for patient-physician shared decision-making,” he said.

The era of immunobiologic therapy was introduced for advanced genitourinary oncology with the approval of sipuleucel-T in 2010, when the IMPACT phase III trial demonstrated a statistically significant survival benefit in patients with metastatic castration-resistant prostate cancer, according to Dr. Shore.

“Since that approval, the science and clinical applications for immune-oncologic therapy have bourgeoned dramatically throughout all of advanced cancer care and research. Hence, it makes great sense to evaluate the application of sip-T, a very well-tolerated therapy, administered over a 4- to 6-week period. [Evaluating the immunotherapy in such a way] does not preclude other approved prostate cancer therapies in order to evaluate its ability to augment the immune system and prevent disease progression for high-risk PSA relapse patients who have failed interventional therapy,” Dr. Shore said.

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While researchers historically use advanced prostate cancer endpoints of overall survival and radiographic progression-free survival, these scientists looked for “PA2024-specific T cell response (Enzyme-Linked ImmunoSPOT [ELISPOT]) over time,” according to the study’s abstract. The study was published online in Clinical Cancer Research (Nov. 10, 2016).

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“As both our biomarker and imaging knowledge advances, it is important to interrogate additional markers, which can be used as appropriate surrogates for clinical and therapeutic decision-making for patients with high-risk disease-albeit whom are earlier in their disease stage. Thus, the immunologic parameters we chose have been widely utilized in other trials for evidence of response and effectiveness,” he said.

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In the study, patients received either sipuleucel-T followed by androgen deprivation therapy or the reverse sequence. PA2024-specific Enzyme-Linked ImmunoSPOT responses were similar between groups, except at week six, when responses were higher in the group receiving the immunotherapy prior to androgen deprivation therapy. Men in both arms showed increased PA2024-specific cellular and humoral responses, and prostatic acid phosphatase-specific humoral responses, which remained higher than baseline for 2 years. Average time-to-PSA recurrence also was similar in both groups.

Sipuleucel-T has become an important part of guideline recommendations in the treatment of men with metastatic castrate-resistant prostate cancer. The National Comprehensive Cancer Network has given sipuleucel-T its highest level of recommendation for specific metastatic castrate-resistant prostate cancer patients. The AUA includes it in its recommendations for castrate-resistant prostate cancer. And on Dec. 21, the Society for Immunotherapy of Cancer published the first evidence-based consensus statement guiding physicians on the use of cancer immunotherapy to treat prostate cancer.

Dr. Shore has research and consulting ties with AbbVie, Amgen, Astellas, Bayer, Dendreon, Ferring, Janssen, Medivation, Moivant, Sanofi-Genzyme, and Tolmar.

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