SWOG-1216: Orteronel vs Bicalutamide With ADT for Metastatic Hormone-Sensitive Prostate Cancer

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As reported in the Journal of Clinical Oncology by Neeraj Agarwal, MD, and colleagues, the phase III SWOG-1216 trial showed no significant improvement in overall survival—the study’s primary endpoint—with orteronel plus androgen-deprivation therapy (ADT) vs bicalutamide plus ADT in patients with newly diagnosed metastatic hormone-sensitive prostate cancer. The orteronel group had significantly prolonged progression-free survival, and postprotocol life-prolonging therapy was received by most patients in both groups.

Orteronel is a nonsteroidal CYP17,20-lyase inhibitor that suppresses androgen synthesis.

Neeraj Agarwal, MD

Neeraj Agarwal, MD

Study Details

In the U.S. open-label multicenter trial, 1,279 eligible patients were randomly assigned between March 2013 and July 2017 to receive continuous ADT (luteinizing hormone-releasing hormone agonist) with either orteronel at 300 mg twice daily (n = 638) or bicalutamide at 50 mg once daily (n = 641). The primary objective was the comparison of overall survival, targeting a 33% improvement in median survival; a stratified log-rank test with a one-sided P ≤ .022 was defined as indicating statistical significance. Progression-free survival and prostate-specific antigen (PSA) level at 7 months were secondary endpoints.

Overall Survival

At the cutoff date for the final analysis after 525 deaths (and 787 progression-free survival events), median follow-up was 4.9 years. Median overall survival was 81.1 months in the orteronel group vs 70.2 months in the control group (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.72–1.02, P = .040). Rates at 5 years were 59.7% vs 57.9%.

Median progression-free survival was 47.6 months in the orteronel group vs 23.0 months in the control group (HR = 0.58, 95% CI = 0.51–0.67, P < .0001), with 4-year rates of 50.2% vs 33.9%. Postprotocol life-prolonging therapy was received by 61.3% of patients in the orteronel group vs 77.4% of patients in the control group.

PSA response at 7 months was significantly better in the orteronel group, with complete response in 58% vs 44% of patients, partial response in 22% vs 31%, and no response in 19% vs 25% (P < .0001).


  • Orteronel plus ADT did not significantly prolong overall survival vs bicalutamide plus ADT.
  • Orteronel plus ADT was associated with significantly improved progression-free survival and PSA response.

Adverse Events

The most common adverse events of any grade in the orteronel group were hot flashes (66.3% vs 69% in control group), fatigue (64.1% vs 46.3%), and hypertension (42.6% vs 13.8%). Grade 3 or 4 adverse events occurred in 43% of the orteronel group vs 14% of the control group; the most common in the orteronel group were hypertension (20.1% vs 4.5%) and fatigue (5.4% vs 1.7%). Adverse events led to death in five patients in the orteronel group and one patient in the control group; causes in the orteronel group included myocardial infarction in two patients and stroke in one.

The investigators concluded, “The study did not meet the primary endpoint of improved overall survival with orteronel. The lack of correlation of progression-free survival and PSA response with overall survival raises concerns over assumption of their consistent surrogacy for overall survival in the context of extensive postprotocol therapy in this setting.”

Dr. Agarwal, of the Genitourinary Oncology Program, Huntsman Cancer Institute, University of Utah, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Cancer Institute and by Millennium Pharmaceuticals, Inc (Takeda Pharmaceutical Company LTD). For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.