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Published on: March 6, 2018
Orteronel Switch Maintenance Therapy in Metastatic Castration Resistant Prostate Cancer After First-Line Docetaxel: A
Richard Cathomas1, Simon J Crabb2, Michael Mark3
1Oncology/Hematology, Kantonsspital Graubünden, Chur, Switzerland. richard.cathomas@ksgr.ch.
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. © 2016 Wiley Periodicals, Inc.
Insights
Orteronel maintenance therapy significantly improved event-free survival (EFS) in men with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel treatment. This suggests switch maintenance therapy is a promising strategy for mCRPC disease control.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Investigating orteronel, an oral androgen biosynthesis inhibitor, as a switch maintenance treatment.
- Evaluating its efficacy in men with metastatic castration-resistant prostate cancer (mCRPC) following docetaxel stabilization.
Purpose of the Study:
- To determine if orteronel maintenance therapy prolongs disease control in mCRPC patients.
- Assessing event-free survival (EFS) as the primary endpoint.
Main Methods:
- Randomized trial comparing orteronel (300 mg twice daily) versus placebo in mCRPC patients with non-progressive disease after docetaxel.
- Primary endpoint: EFS (death or radiographic, clinical, or PSA progression).
Main Results:
- The trial was closed early with 47 patients randomized.
- Orteronel significantly improved median EFS (8.5 vs. 2.9 months; P=0.001) and radiographic progression-free survival (rPFS).
- Higher PSA decline rates (≥50%) observed with orteronel (57% vs. 4%); toxicity was generally mild.
Conclusions:
- Orteronel demonstrated a significant prolongation of EFS in mCRPC patients stabilized on docetaxel.
- The study supports the potential of switch maintenance therapy in mCRPC management.
- Further research into mCRPC switch maintenance strategies is warranted.
