Immunotherapy in intermediate-risk biochemically recurrent prostate cancer (BCR): The National Cancer Institute experience.

Abstract

170 Background: Androgen receptor (AR) targeting strategies have demonstrated clinical impact in high-risk BCR (e.g., PSA DT<6 months (mos)) but are associated with significant toxicities. Given the median age of BCR ≥70 years (yrs) and a low risk of death from prostate cancer, patients (pts) with intermediate risk BCR (e.g. PSA DT 6-15 mos) may not require intervention with AR-based treatment and may avoid associated toxicities. The NCI has conducted 2 BCR studies that highlight the potential of immunotherapy in intermediate-risk BCR. Methods: NCT02649439 evaluated PROSTVAC, a pox virus-based immunotherapy, targeting PSA in men with BCR. NCT03315871 evaluated PROSTVAC and CV-301 (a pox virus-based immunotherapy strategy targeting CEA and MUC-1). Both trials had the same eligibility criteria of PSA >0.8 ng/mL post-RP or >2.0 ng/mL after RT, PSADT 5-15 mos; testosterone >100 ng/dL, and negative CT and bone scan. Serial PSA levels were measured, and responses were defined as confirmed declines from an intra-study peak (ISAP) PSA (Madan RA, et al, ASCO GU, 2018). NCT03315871 also employed pre- and post-treatment prostate specific membrane antigen (PSMA) imaging that assessed for PSMA tumor volume (PSMA-TV). Given the similar study designs, treatments and eligibility, these data from these 2 studies are combined in this analysis. Results: A total of 96 BCR pts were treated with immunotherapy in both studies and evaluable for responses. Median baselines included: age 67.5 yrs (range 53.5-83.5), PSA 3.5 ng/dL (0.83-32.9), and Gleason score 7 (4-10). Adverse events were minimal and self-limiting, including injection-site reactions, flu-like symptoms, myalgias, and arthralgias. Among evaluable pts, ISAP PSA declines occurred in 28/96 (29%) pts with a median decline of 19% (11-99%). PSA declines occurred at a median of 77 days (range 0-553) after immunotherapy and lasted a median of 140 days (range 56-1500+). In NCT03315871, 21 pts had pre- and post-treatment PSMA imaging. Decreases in PSMA-TV after treatment were seen in 9/21 (43%) pts after PROSTVAC and CV-301, and all 9 pts had PSA declines or stabilization after immunotherapy. Conclusions: Both NCT02649439 and NCT03315871 evaluated antigen-directed immunotherapy in intermediate-risk BCR without ADT. These data suggest there is potential for immunotherapy (beyond immune checkpoint inhibitors) to delay PSA kinetics in BCR. PSMA-TV response data in NCT03315871 suggest immunotherapy-associated PSA responses impact tumor volume. Immunotherapy may have the ability to impact BCR with minimal toxicity while slowing disease trajectory in intermediate-risk BCR and substantially delaying or diminishing the need for other therapies and associated toxicities in this patient population. Further immunotherapy trials in BCR without ADT are ongoing at the NCI. Clinical trial information: NCT03315871 , NCT02649439 .