Orteronel fails to improve overall survival in metastatic prostate cancer: Study

USA: For patients with newly diagnosed metastatic hormone-sensitive prostate cancer, the addition of orteronel to androgen deprivation therapy (ADT) significantly improves progression-free survival but not overall survival (OS). The study has been published in the Journal of Clinical Oncology.

Prostate cancer is a major health issue, with approximately 1.3 million new cases diagnosed worldwide each year. Metastatic hormone-sensitive prostate cancer (mHSPC) is cancer that has spread past the prostate into the body but can be treated with hormone therapy. The revolution in the management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) began recently with the addition of novel systemic therapies to androgen deprivation therapy (ADT). Orteronel (TAK-700) is an investigational, nonsteroidal 17,20-lyase inhibitor suppressing androgen synthesis.

Neeraj Agarwal, University of Utah Huntsman Cancer Institute, Utah, USA, and his team conducted an open-label randomized phase III trial to evaluate the clinical benefit of orteronel when added to androgen deprivation therapy (ADT) in patients with newly diagnosed metastatic hormone-sensitive prostate cancer.

Researchers enrolled 1,279 patients (median age was 68 years; 49% with extensive disease) with metastatic hormone-sensitive prostate cancer and randomly assigned them 1:1 to ADT with orteronel (300 mg orally twice daily; n=638 experimental arm) or ADT with bicalutamide (50 mg orally once daily; n=641 control arm). The primary endpoint 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 endpoints 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.

Key findings of the study,

• There was a significant improvement in PFS (median 47.6 v 23.0 months, HR- 0.58) and PSA response at 7 months, but not in OS (median 81.1 v 70.2 months, HR -0.86).

• More grade 3/4 adverse events occurred in the experimental versus the control arms (43% v 14%).

• Post protocol life-prolonging therapy was received by 77.4% of patients in the control arm and 61.3% of patients in the orteronel arm.

The authors conclude that the addition of orteronel to ADT resulted in a significant improvement in progression-free survival and prostate-specific antigen response but not in overall survival (OS), the primary endpoint. The median OS of patients in the control arm was higher than that in patients with metastatic hormone-sensitive prostate cancer who had similar disease severity and also received ADT plus bicalutamide.

Reference:

Neeraj Agarwal, Catherine M. Tangen, Maha H.A. Hussain, Shilpa Gupta, Melissa Plets et al.Journal of Clinical Oncology 0 0:0 Orteronel for Metastatic Hormone-Sensitive Prostate Cancer: A Multicenter, Randomized, Open-Label Phase III Trial (SWOG-1216)  DOI https://doi.org/10.1200/JCO.21.02517