Orteronel for Metastatic Hormone-Sensitive Prostate Cancer: A Multicenter, Randomized, Open-Label Phase III Trial (SWOG-1216).

Autor:	Agarwal N; University of Utah Huntsman Cancer Institute, Salt Lake City, UT., Tangen CM; SWOG Statistics and Data Management Center, Seattle, WA., Hussain MHA; Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, IL., Gupta S; Cleveland Clinic Taussig Cancer Institute, Cleveland, OH., Plets M; SWOG Statistics and Data Management Center, Seattle, WA., Lara PN; UC Davis Comprehensive Cancer Center, Sacramento, CA., Harzstark AL; Kaiser Permanente-Oakland, Oakland, CA., Twardowski PW; John Wayne Cancer Institute, Santa Monica, CA., Paller CJ; Johns Hopkins University School of Medicine, Baltimore, MD., Zylla D; Metro Minnesota CCRC/Park Nicollet Clinic, St Louis Park, MN., Zibelman MR; Fox Chase Cancer Center, Philadelphia, PA., Levine E; Roswell Park Comprehensive Cancer Center, Buffalo, NY., Roth BJ; Washington University School of Medicine, St Louis, MO., Goldkorn A; USC, Norris Comprehensive Cancer Center, Los Angeles, CA., Vaena DA; University of Iowa, Iowa City, IA.; West Cancer Center, Germantown, TN., Kohli M; University of Utah Huntsman Cancer Institute, Salt Lake City, UT.; Mayo Clinic at Rochester, Rochester, MN., Crispino T; UsTOO Prostate Cancer Support and Education Las Vegas Chapter, Las Vegas, NV., Vogelzang NJ; Comprehensive Cancer Centers of Nevada, Las Vegas, NV., Thompson IM Jr; CHRISTUS Santa Rosa Health System, San Antonio, TX., Quinn DI; USC, Norris Comprehensive Cancer Center, Los Angeles, CA.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2022 Oct 01; Vol. 40 (28), pp. 3301-3309. Date of Electronic Publication: 2022 Apr 21.
DOI:	10.1200/JCO.21.02517
Abstrakt:	Purpose: Orteronel (TAK-700) is a nonsteroidal 17,20-lyase inhibitor suppressing androgen synthesis. We evaluated the clinical benefit of orteronel when added to androgen deprivation therapy (ADT) in patients with newly diagnosed metastatic hormone-sensitive prostate cancer. Methods: In this open-label randomized phase III study, patients with metastatic hormone-sensitive prostate cancer were randomly assigned 1:1 to ADT with orteronel (300 mg oral twice daily; experimental arm) or ADT with bicalutamide (50 mg oral once daily; control arm). The primary objective was the comparison of overall survival (OS), targeting a 33% improvement in median survival. A stratified log-rank test with a one-sided P ≤ .022 would indicate statistical significance. Secondary end points were progression-free survival (PFS), prostate-specific antigen (PSA) level at 7 months (≤ 0.2 v 0.2 to ≤ 4 v > 4 ng/mL), and adverse event profile. Results: Among 1,279 patients included in the analysis, 638 were randomly assigned to the ADT plus orteronel arm and 641 to the control arm. The median age was 68 years; 49% had extensive disease. After a median follow-up of 4.9 years, there was a significant improvement in PFS (median 47.6 v 23.0 months, hazard ratio 0.58; 95% CI, 0.51 to 0.67; P < .0001) and PSA response at 7 months ( P < .0001), but not in OS (median 81.1 v 70.2 months, hazard ratio 0.86; 95% CI, 0.72 to 1.02; P = .040, one-sided). More grade 3/4 adverse events occurred in the experimental versus the control arms (43% v 14%). Postprotocol life-prolonging therapy was received by 77.4% of patients in the control arm and 61.3% of patients in the orteronel arm. Conclusion: The study did not meet the primary end point of improved OS with orteronel. The lack of correlation of PFS and PSA response with OS raises concerns over assumption of their consistent surrogacy for OS in the context of extensive postprotocol therapy in this setting.
Databáze:	MEDLINE
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