Richard Cathomas1, Simon J Crabb2, Michael Mark3, Ralph Winterhalder4, Christian Rothermundt5, Tony Elliott6, Philippe von Burg7, Heike Kenner8, Stefanie Hayoz8, Simona Berardi Vilei8, Daniel Rauch9, Enrico Roggero10, Markus G Mohaupt11, Jürg Bernhard12, Gabriela Manetsch3, Silke Gillessen5. 1. Oncology/Hematology, Kantonsspital Graubünden, Chur, Switzerland. richard.cathomas@ksgr.ch. 2. Cancer Sciences Unit, University of Southampton, Southampton, United Kingdom. 3. Oncology/Hematology, Kantonsspital Graubünden, Chur, Switzerland. 4. Department of Oncology Kantonsspital Luzern, Luzern, Switzerland. 5. Department of Oncology/Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland. 6. Department of Oncology, The Christie Clinic, Manchester, United Kingdom. 7. Department of Oncology, Kantonsspital Aargau, Aarau, Switzerland. 8. SAKK Coordinating Center, Bern, Switzerland. 9. Oncology, Hospital Simmental, Thun, Switzerland. 10. Department of Oncology, Bellinzona IOSI, Bellinzona, Switzerland. 11. Department of Nephrology, Hypertension and Clinical Pharmacology, University of Bern, Bern, Switzerland. 12. International Breast Cancer Study Group Coordinating Center Bern and University Hospital, Inselspital Bern, Switzerland.
Abstract
BACKGROUND: We tested whether a switch maintenance treatment with orteronel, an oral inhibitor of androgen biosynthesis, prolongs disease control in men with metastatic castration-resistant prostate cancer (mCRPC) after documented disease stabilization with docetaxel. METHODS:Men with mCRPC and non-progressive disease after a cumulative dose of ≥300 mg/m2 docetaxel for first line treatment were randomized 1:1 to receive orteronel 300 mg twice daily or placebo. The primary endpoint was event-free survival (EFS) defined as the time from randomization to death or the combination of at least two of radiographic, clinical, or PSA progression. Ninety-six patients per arm were planned to demonstrate an improvement of median EFS from 4 months on placebo to 6.7 months on orteronel (hazard ratio (HR) 0.6; type I error 5% and power 90%). RESULTS:Forty-seven patients (23 orteronel, 24placebo) were randomized before premature closure of the trial because of discontinuation of clinical development of orteronel. Median EFS was 8.5 months with orteronel and 2.9 months with placebo (P = 0.001; HR 0.32; 95%CI 0.15-0.65). Median radiographic progression-free survival (rPFS) was 8.5 and 2.8 months (P = 0.02; HR 0.42; 95%CI 0.20-0.91) in the orteronel and placebo arm, respectively. PSA decline ≥50% was seen in 57% on orteronel and 4% on placebo. Toxicity was mainly mild, one patient on orteronel developed transient grade 3 adrenal insufficiency and one grade 4 pneumonitis. CONCLUSIONS: Orteronel significantly prolongs EFS in men with mCRPC who achieve disease stabilization with docetaxel. The concept of switch maintenance therapy in mCRPC warrants further research. Prostate 76:1519-1527, 2016.
RCT Entities:
BACKGROUND: We tested whether a switch maintenance treatment with orteronel, an oral inhibitor of androgen biosynthesis, prolongs disease control in men with metastatic castration-resistant prostate cancer (mCRPC) after documented disease stabilization with docetaxel. METHODS:Men with mCRPC and non-progressive disease after a cumulative dose of ≥300 mg/m2 docetaxel for first line treatment were randomized 1:1 to receive orteronel 300 mg twice daily or placebo. The primary endpoint was event-free survival (EFS) defined as the time from randomization to death or the combination of at least two of radiographic, clinical, or PSA progression. Ninety-six patients per arm were planned to demonstrate an improvement of median EFS from 4 months on placebo to 6.7 months on orteronel (hazard ratio (HR) 0.6; type I error 5% and power 90%). RESULTS: Forty-seven patients (23 orteronel, 24 placebo) were randomized before premature closure of the trial because of discontinuation of clinical development of orteronel. Median EFS was 8.5 months with orteronel and 2.9 months with placebo (P = 0.001; HR 0.32; 95%CI 0.15-0.65). Median radiographic progression-free survival (rPFS) was 8.5 and 2.8 months (P = 0.02; HR 0.42; 95%CI 0.20-0.91) in the orteronel and placebo arm, respectively. PSA decline ≥50% was seen in 57% on orteronel and 4% on placebo. Toxicity was mainly mild, one patient on orteronel developed transient grade 3 adrenal insufficiency and one grade 4 pneumonitis. CONCLUSIONS:Orteronel significantly prolongs EFS in men with mCRPC who achieve disease stabilization with docetaxel. The concept of switch maintenance therapy in mCRPC warrants further research. Prostate 76:1519-1527, 2016.
Authors: K Fizazi; A Ulys; L Sengeløv; M Moe; S Ladoire; A Thiery-Vuillemin; A Flechon; A Guida; J Bellmunt; M A Climent; S Chowdhury; H Dumez; M Matouskova; N Penel; S Liutkauskiene; L Stachurski; C N Sternberg; F Baton; N Germann; G Daugaard Journal: Ann Oncol Date: 2017-11-01 Impact factor: 32.976