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While many approaches to using immunotherapy for the treatment of prostate cancer are under study, four strategies currently in later-stage clinical development have emerged as the most promising.
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Leonard G. Gomella, MD, discusses immunotherapy.
While many approaches to using immunotherapy for the treatment of prostate cancer are under study, four strategies currently in later-stage clinical development have emerged as the most promising advances in the field thus far, according to Leonard G. Gomella, MD.
These agents are coming into focus at a time when immunotherapy is an increasingly accepted approach to the treatment of prostate cancer. Gomella anticipates that new immunotherapies will become available in the next several years, and that treatment issues will increasingly focus on how to combine and sequence modalities.
Gomella, who served as a program director for the IPCC conference, is chair of the Department of Urology and director of Clinical Affairs at the Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
He said that prostate cancer makes a good target for immunotherapy for several reasons, including a slowgrowing nature that gives the patient’s immune system time to generate a response and the multiple tissue-specific proteins that could serve as prostate tumor antigens.
“We did come over a hurdle about 10 years ago in prostate cancer, realizing from a molecular standpoint and from a proteomic and immunologic standpoint that you could stimulate the immune system to recognize prostate cells or turn on the immune system in order to fight advanced prostate cancer,” Gomella said in an interview during IPCC. “All these things are very exciting and I think where we’re going to be looking at all these immunotherapeutic agents in the next five years will concern sequencing.”
He identified studies involving these agents as the most noteworthy (Table):
3 mo ADT + sipuleucel-T
3 mo ADT + control
BF, DF, OS, PSADT
Sipuleucel-T x 3 prior to RP + post-op booster vs Sipuleucel-T x 3 prior to RP + no booster
Immune response, safety
Asymptomatic or minimally symptomatic CRPC
Sipuleucel-T at 3 different concentrations of PA2024 antigens
CD54 upregulation, immune response, OS
High-risk, nonmetastatic CRPC
177Lu-J591 + ketoconazole + hydrocortisone vs 111In-J591 (placebo) + ketoconazole + hydrocortisone
PFS, OS, PSA, RECIST
Weill Cornell Medical College
CRPC post docetaxel
XRT + ipilumumab vs XRT + placebo
OS, PFS, pain, safety
PROSTVAC-VF-TRICOM + GM-CSF vs PROSTVAC-VF-TRICOM + GM-CSF placebo vs Vector placebo + GM-CSF placebo
OS, event-free progression
ADPC indicates androgen-dependent prostate cancer; ADT, androgen-deprivation therapy; BF, biochemical failure; CRPC, castration-resistant prostate cancer;
DF, distant metastatic disease; GM-CSF, granulocyte-macrophage colony stimulating factor; PC, prostate cancer; PFS, progression-free survival; PSA, prostatespecific antigen; PSADT, PSA doubling time; OS, overall survival; RECIST, response evaluation criteria in solid tumors; RP, radical prostatectomy; XRT, radiotherapy.
PROSTVAC is a sequentially dosed combination of two poxviruses, Vaccinia and Fowlpox, each encoded with PSA plus TRICOM (three costimulatory molecules [B7.1, ICAM-1, and Lfa-3]). The first poxvirus is Vaccina-PSA-TRICOM; the second is Fowlpox-PSA-TRICOM.
Adapted from Gomella LG. Current and emerging immunotherapy strategies for prostate cancer. Presented at: 5th Annual Interdisciplinary Prostate Cancer Congress (IPCC); March 31, 2012; New York, NY.
Of these approaches, Gomella said in an interview that “we really have three that look like the hot things:” sipuleucel-T, ipilumumab, and PROSTVAC. “Sipuleucel-T being FDA-approved now for almost two years and being used clinically is a great thing to have for our patients,” he said. “Ipilimumab is showing very significant activity in prostate cancer so that one is very exciting. And lastly, the PROSTVAC-V TRICOM studies are going to be very interesting.”
He said ipilimumab and PROSTVAC are administered through injections, and thus offer more convenience than the leukapheresis process needed with sipuleucel-T.
One challenge going forward will be to evaluate responses to immunotherapies. A decline in PSA levels, for example, is not a reliable method of determining responses to sipuleucel-T or pox-based vectors, and evidence is mixed about PSA’s predictive value with ipilimumab, Gomella indicated in his presentation.
“We need new markers to study these things,” Gomella said. “What probably happens with immunotherapies is that there is a slow, long-term response that the body generates to fight the cancer, as opposed to cytotoxic chemotherapy where you get a big hit. With immunotherapy, you probably get a brake put on the cancer and, while you may not quote ‘cure’ anybody, you’re certainly slowing down the progression.”