Following the success of an innovative Phase 1b trial exploring adaptive androgen deprivation therapy (ADT) in men with metastatic castration-sensitive prostate cancer (mCSPC), researchers are now expanding their approach in a Phase 2 study that incorporates docetaxel into the treatment regimen.

The Phase 1b trial was a pivotal step in redefining how ADT is administered. Traditionally, continuous hormone therapy has been the cornerstone of managing advanced prostate cancer, but it often comes with significant long-term side effects, including fatigue, bone loss, and cognitive decline. To address these challenges, the trial introduced a dynamic, intermittent therapy model. Men with mCSPC began treatment with an LHRH analog and a new hormonal agent (abiraterone, enzalutamide, or apalutamide) until achieving a PSA reduction of over 75%. At that point, treatment was paused and resumed based on individual PSA and testosterone levels, guided by an adaptive algorithm.

The results were compelling. At 12 months, none of the 16 participants experienced radiographic disease progression, confirming the feasibility of this adaptive approach. Moreover, after a median follow-up of 26 months, the secondary endpoints—median time to PSA and radiographic progression—remained unreached, indicating durable disease control. Patients who achieved a complete response during the induction phase appeared to benefit most, and the intermittent therapy approach significantly mitigated the toxicities typically associated with continuous ADT.

Building on this foundation, the ongoing Phase 2 trial seeks to enhance the benefits of adaptive therapy by adding docetaxel, a chemotherapy agent known to extend survival in mCSPC. This trial adopts a similar patient-centric approach, using PSA responses to guide the timing and combination of treatments, which include LHRH analogs, androgen receptor signal inhibitors (ARSIs), and docetaxel. The hypothesis driving this study is that adaptive therapy, when combined with docetaxel, can prolong the castration-sensitive phase of stage IV prostate cancer, potentially delaying progression and further improving outcomes.

This second-phase study is designed as a single-arm trial, with all participants receiving the same adaptive treatment protocol. Inclusion criteria ensure the selection of patients who are likely to respond to the adaptive approach, such as those who achieve significant PSA reductions during a preliminary run-in phase. Regular monitoring ensures that the therapy is adjusted in real time to optimize both efficacy and tolerability.

Source.

Clinical trial.