The first FDA-approved prostate cancer vaccine was Sipuleucel-T. On Day 1, leukopheresis is performed at the apharesis center, Day 2-3 Sipuleucel-T is manufactured by the company, and Day 3-4 the patient is infused in the doctor’s office. Sipuleucel-T received approval based off of results from the IMPACT trial which demonstrated a median survival benefit of 4.1 months and HR for OS of 0.775 (95%CI 0.61-0.98) among men with mCRPC for Sipuleucel-T compared to placebo . Based on the Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of prostate carcinoma in December 2016 , the expert panel recommends using Sipuleucel-T early and in less aggressive disease.
More recently has been the development of the PROSTVAC-VF (PSA-TRICOM) DNA vaccine composed of the PSA tumor antigen gene and a triad of co-stimulatory molecules. In a phase II study assessing efficacy of this DNA vaccine, there was an 8.5 month improved OS compared to placebo (16.6 vs 25.1 months), with a HR of 0.56 (95%CI 0.37-0.85) . Based on this, a phase III study was designed for asymptomatic/minimally symptomatic men with mCRPC randomized 400 patients to each arm of: PROSTVAC-V/F + GM-CSF vs PROSTVAC- V/F vs vector placebo. Patients will be followed every 6 months for 5 years and the primary outcome is OS. The study has accrued well (n=1,297), with a 6.1 mean number of injections; an increased number of injections compared to the phase II trial (5.4 inj) is expected to improve clinical outcomes in the treatment arm. At this point in time, the OS results are not unblended as of yet, however the blinded complete cohort OS is 33.9 months, akin to prior mCRPC pre-chemo OS results.
Dr. Gully concluded his presentation with several take-home message points: (i) T-cell poor tumors may require a ‘spark’ to get the immune system to recognize and seek to destroy the tumor, and one way to do this is with a vaccine, (ii) Sipuleucel-T is approved in the US and unblinded data from the PSA-TRICOM study is anticipated soon, (iii) approaches that both steer the immune system and allow effector cells to get to and remain functional within the tumor microenvironment will be optimal.
Speaker: James Gulley, National Cancer Institute, Bethesda, MD, United States of America
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain
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2. McNeel DG, Bander NH, Beer TM, et al. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of prostate carcinoma. Journal of ImmunoTherapy of Cancer 2016;4:92.
3. Kantoff PW, Schuetz TJ, Blumenstein BA, et al. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol 2010;28(7):1099-1105.