TY - JOUR
T1 - Orteronel for Metastatic Hormone-Sensitive Prostate Cancer
T2 - A Multicenter, Randomized, Open-Label Phase III Trial (SWOG-1216)
AU - Agarwal, Neeraj
AU - Tangen, Catherine M.
AU - Hussain, Maha H.A.
AU - Gupta, Shilpa
AU - Plets, Melissa
AU - Lara, Primo N.
AU - Harzstark, Andrea L.
AU - Twardowski, Przemyslaw W.
AU - Paller, Channing J.
AU - Zylla, Dylan
AU - Zibelman, Matthew R.
AU - Levine, Ellis
AU - Roth, Bruce J.
AU - Goldkorn, Amir
AU - Vaena, Daniel A.
AU - Kohli, Manish
AU - Crispino, Tony
AU - Vogelzang, Nicholas J.
AU - Thompson, Ian M.
AU - Quinn, David I.
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - PURPOSEOrteronel (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.METHODSIn 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.RESULTSAmong 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.CONCLUSIONThe 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.
AB - PURPOSEOrteronel (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.METHODSIn 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.RESULTSAmong 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.CONCLUSIONThe 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.
UR - http://www.scopus.com/inward/record.url?scp=85130136111&partnerID=8YFLogxK
U2 - 10.1200/JCO.21.02517
DO - 10.1200/JCO.21.02517
M3 - Article
C2 - 35446628
AN - SCOPUS:85130136111
SN - 0732-183X
VL - 6
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
M1 - JCO.21.02517
ER -