Phase III trial of dose escalated radiation therapy and standard androgen deprivation therapy (ADT) vs. dose escalated radiation therapy and enhanced ADT with orteronel for men with high-risk prostate cancer (NRG/RTOG 1115)
Mené sur 231 patients atteints d’un cancer de la prostate à haut risque (durée médiane de suivi : 6,2 ans), cet essai randomisé de phase III évalue l'efficacité, du point de vue de la survie globale, d'un ajout d'ortéronel (un inhibiteur du CYP17A1) au traitement combinant radiothérapie et thérapie anti-androgénique
Objective: NRG/RTOG 1115 was a phase III trial evaluating the addition of orteronel, a CYP17A1 inhibitor, to radiation therapy (RT) plus androgen deprivation therapy (ADT) in men with high-risk prostate cancer.
Methods; The study was designed to evaluate overall survival (OS) for 900 men with high-risk prostate cancer (Gleason 9-10, PSA > 20, or clinical stage T2 or higher with Gleason ≥ 8). Patients were randomized 1:1 to standard therapy (RT plus 2 years of ADT) or standard therapy plus 2 years of orteronel. RT entailed image-guided conventionally fractionated dose-escalated external beam radiation to the prostate and pelvis to 45 Gy using intensity-modulated RT (IMRT) with either IMRT (to 79.2 Gy) or brachytherapy boost. Health-related quality of life (HRQOL) was measured using the EPIC-26, PROMIS, and EQ-5D. Accrual was halted early due to discontinuation of orteronel development and the trial redesigned to focus on a composite biochemical failure endpoint.
Results: There were a total of 231 eligible randomized patients. Only 29% in the orteronel arm received ≥80% of the planned dose. With median follow-up of 6.2 years, the cumulative incidence of grade 3+ adverse events was higher on orteronel than on the standard arm (p<0.001, hazard ratio [HR: 2.32 (95% CI: 1.52-3.47)]) with 5-year estimates of 59.0% and 35.1%, respectively. No significant differences in OS (p=0.28, HR:0.71 (95% CI:0.39-1.32) or BF (p=0.56, HR 0.84, 95% CI 0.47-1.51) were observed. Use of orteronel had a transient negative impact upon all prostate cancer-specific QOL domains of the EPIC-26, but did not increase the magnitude of decline once RT started and had minimal impact upon other HRQOL measures.
Conclusions: The addition of orteronel to RT and ADT did not result in significant improvement in any efficacy outcomes, although information was limited by poor drug tolerance and early termination of accrual thus limiting statistical power.
International Journal of Radiation Oncology, Biology, Physics , article en libre accès, 2025