Efficacy Results: rPFS and Overall Survival in ARASEC

The phase 2 ARASEC trial (NCT02799602), met its primary end point, demonstrating a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) with darolutamide (Nubeqa) plus androgen deprivation therapy (ADT) compared with the propensity score–matched ADT monotherapy control arm from CHAARTED (NCT02799602). Rana R. McKay, MD, FASCO, reported an HR of 0.29—representing a 71% reduction in the risk of radiographic progression or death. McKay first addressed a key stipulated limitation: Because CHAARTED accrued in the early 2000s, post-protocol therapies and the overall treatment landscape had evolved substantially, prompting a post hoc sensitivity analysis using the contemporaneous ADT monotherapy arm from the ARANOTE trial (NCT04736199).

The ARANOTE sensitivity analysis yielded a consistent rPFS benefit and an overall survival (OS) HR of 0.55, compared with an HR of 0.50 in the primary CHAARTED-referenced analysis—both statistically significant results. McKay highlighted that approximately 65% of patients in the ADT monotherapy control arm went on to receive subsequent therapy after progression, vs a markedly lower proportion in the darolutamide arm. This imbalance in post-protocol treatment, which would be expected to attenuate the observed OS difference, makes the statistically significant survival benefit in the darolutamide arm all the more notable. Neal D. Shore, MD, FACS, noted that faster progression in the control arm, and therefore greater uptake of subsequent therapies, is a pattern consistent with what has been observed across comparable trials.

Shore contextualized the ARASEC efficacy results within the established darolutamide evidence base, noting that ARAMIS (NCT02200614) and ARASENS (NCT02799602) had already demonstrated OS benefits in nmCRPC and the triplet mHSPC setting, respectively. He characterized the ARASEC findings not as redundant but as a validation of darolutamide's efficacy in a prospective US population—reinforcing, rather than simply repeating, what the broader trial program had shown. The convergence of rPFS and OS signals across both the primary and sensitivity analyses further strengthens confidence in the clinical meaningfulness of the results.

REFERENCE

1. McKay RR, Ross AE, Preston MA, et al. ARASEC: A novel pragmatic trial design comparing darolutamide plus ADT versus ADT in US patients with metastatic hormone-sensitive prostate cancer using propensity score matching with an external phase 3 trial control arm. J Urol. 2025;213(5S). doi:10.1097/01.JU.0001109788.ARASEC