ENZALUTAMIDE, an oral androgen receptor inhibitor, has demonstrated significant clinical benefit in men with metastatic hormone-sensitive prostate cancer (mHSPC), particularly when used in combination with androgen deprivation therapy (ADT). Findings from the pivotal ARCHES trial revealed that enzalutamide plus ADT significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) compared to placebo plus ADT.
A post hoc analysis of the ARCHES trial has now provided further insight into the relationship between prostate-specific antigen (PSA) responses and long-term outcomes. The data showed that 68.1% of patients receiving enzalutamide achieved undetectable PSA levels (<0.2 ng/mL), compared to only 17.6% in the placebo group. Importantly, PSA decline was strongly associated with improved survival outcomes, reinforcing its role as a reliable prognostic marker.
The analysis also highlighted that treatment intensification with enzalutamide benefited patients regardless of baseline PSA or prior response to ADT. Notably, even patients who initially responded well to ADT alone saw improved rPFS and OS when enzalutamide was added. This finding suggests that a favourable early PSA response should not discourage the addition of enzalutamide.
Furthermore, patients who achieved a PSA reduction to below 4 ng/mL at six months, or undetectable PSA levels, had significantly reduced risks of disease progression and death. These results are consistent with other major trials, including TITAN, ARASENS, and PREVAIL, which also showed that deeper PSA declines correlate with better outcomes across different prostate cancer settings.
Enzalutamide led to rapid and sustained PSA responses, with the median time to undetectable PSA being just over five months. Patients achieving such deep responses also reported fewer musculoskeletal events and fatigue, indicating a more tolerable treatment course.
In conclusion, enzalutamide plus ADT offers substantial survival advantages in men with mHSPC, irrespective of PSA level at enrolment or prior ADT response. These findings support its broader use as a key component in the treatment landscape for advanced prostate cancer.
Reference
Azad AA et al. Enzalutamide and prostate-specific antigen levels in metastatic prostate cancer: a secondary analysis of the ARCHES randomized clinical trial. JAMA Netw Open. 2025;8(5):e258751.
