A phase 1b adaptive androgen deprivation therapy trial in metastatic castration sensitive prostate cancer.

5075 Background: Despite early utilization of new hormonal agents (NHA, abiraterone, enzalutamide and apalutamide) in metastatic castration sensitive prostate cancer (mCSPC), increasingly more men are dying from prostate cancer. While continued development of new drugs is needed, we propose improved survival of metastatic prostate cancer can be obtained through tumor evolution informed treatment strategies. Compared to the conventional treat until progression paradigm, our previous study (NCT02415621) in metastatic castration resistant prostate cancer reported that on and off abiraterone therapy adapted to individual’s PSA response dynamics can provide better cancer control with less abiraterone usage (Zhang et al, Nat Commun. 2017). Here we present the first interim analysis of our adpative therapy trial in mCSPC with a median follow up of 21 months. Methods: Men with asymptomatic mCSPC and no liver metastasis were enrolled after achieved > 75% PSA decline with 12 - 16 weeks of luteinizing hormone-releasing hormone (LHRH) analog, and 8 - 12 weeks of NHA. Both treatments were stopped after enrollment. PSA and testosterone levels were measured every 6 weeks, CT and bone scan were performed every 18 weeks while on study. Treatment will be restarted if subjects develop PSA or radiographic progression per prostate cancer working group 3 criteria. If the testosterone level (T) is > 100 ng/dl, LHRH analog will be restarted. If the T is between 50 and 100 ng/dl, NHA will be restarted. If the T is below 50, combined therapy with LHRH analog and NHA will be restarted. Treatment will be discontinued after achieving 50% or more PSA decline. For patients who restarted therapy for radiographic progression, partial response or stable disease needs to be documented on the post treatment scans along with PSA response prior to stopping therapy. The primary objective is feasibility, which is measured by percentage of patients who remain on study without on treatment disease progression at 12 months from first dose of LHRH analog for mCSPC. Results: 16 evaluable patients were enrolled between April 2019 and June 2021. Five of the 16 patients had high risk mCSPC based on the LATITUDE trial criteria. The median follow up was 21 months at the data cut off in January 2022. Only one patient was off study due to imaging progression at 27.6 months from first dose of LHRH analog for mCSPC. Three of the 16 patients developed on treatment PSA progression at month 12.3 and 15.2, and 20.5. Given none of the first 14 enrolled patients developed disease progression at 12 months, the study has already met its primary objective of feasibility. Conclusions: It is feasible to use individual’s PSA response and testosterone level to guide intermittent therapy with LHRH analog and NHA in mCSPC. The study is ongoing to collect data on secondary endpoints of median time to PSA progression and median time to radiographic progression. Clinical trial information: NCT 03511196.