Exploratory biomarker analysis for progression during adaptive androgen deprivation therapy for metastatic castration sensitive prostate cancer.

Abstract

e17095 Background: When cure is not feasible, adaptive therapy can provide better control of metastatic cancer by delaying the evolution of treatment resistance. For patients with metastatic castrate sensitive prostate cancer (mCSPC), we previously reported on the feasibility of using serum total PSA and testosterone levels to decide when to stop and restart androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone analog (LHRHa) and or a new hormonal agent (NHA) like abiraterone or apalutamide (PMID: 36358643). Here we provide an updated analysis of this pilot study with a median follow-up of 52 months. Methods: Patients (pts) with mCSPC and no liver metastases were consented and enrolled after achieving 75% or more PSA decline after 8-12 weeks of an induction phase with LHRHa plus NHA. Both LHRHa and NHA were discontinued after study enrollment. PSA and testosterone were monitored every 6 weeks. CT and bone scans were performed every 18 weeks. ADT was restarted when pts developed off treatment PSA or imaging progression. The choice of LHRHa versus NHA versus LHRHa plus NHA was based on testosterone levels. ADT was stopped again after 50% or more PSA decline. Pts were taken off the study when they developed radiographic progression while on LHRHa and NHA. One-way ANOVAs provided exploratory biomarker analyses. Results: 6 of the 16 enrolled patients had on-treatment PSA progression and 4 of the 6 had progressed radiographically at 25, 27.6, 28, 28.3 months from the first LHRHa injection for mCSPC. Exploratory biomarker analyses compared baseline characteristics, PSA and testosterone kinetics between the 3 pts with early (12-21 months) PSA progression (E), 3 pts with late (26-43 months) PSA progression (L) and the 10 pts with no PSA progression (N) (46-68 months of follow up). We also calculated the average PSA/testosterone ratio (ave P/T) from a patient’s measurements between the start of the induction phase and restarting ADT for the first time during adaptive therapy. Among the 3 groups, the E group had the highest post induction PSA value (PIP), highest ave P/T and the highest number of metastases (Mets). As shown in table 1, PIP had the strongest association with PSA and radiographic progression. This was followed by ave P/T. Conclusions: Adaptive therapy based on serum PSA and testosterone levels is feasible for mCSPC. High PIP and high ave P/T level are significantly associated with early PSA and radiographic progression in our exploratory analyses. These biomarkers are being tested to improve adaptive therapy in our new mCSPC study (NCT06734130). Clinical trial information: NCT03511196 . Categories Gleason Group # Mets # Bone Mets PIP Ave P/T PSA progression (E+L vs N) P = 0.21 P = 0.023 P = 0.016 P = 0.011 P = 0.014 PSA progression (E vs L vs N) P = 0.28 P = 0.034 P = 0.05 P = 0.000041 P = 0.0014 Radiographic Progression P = 0.096 P = 0.6 P = 0.2 P = 0.00022 P = 0.0017