Metastatic Prostate Cancer OS Up Markedly

The S1216 study was conducted by researchers from SWOG Cancer Research Network, a cancer clinical trials group funded by the National Cancer Institute (NCI). It tested the efficacy of the drug orteronel in these patients, pairing it with androgen deprivation therapy on the investigational arm and comparing that combination to androgen deprivation therapy plus bicalutamide. The results are published in the Journal of Clinical Oncology. 

Although the study missed the primary endpoint of a 33 percent improvement in overall survival (OS), it also showed an unprecedented median OS of 70 months in the control arm, the highest ever reported for these patients on a non-intensified androgen deprivation therapy arm. This OS is a 24 month improvement over results reported in 2013 from the SWOG-9346 trial, which enrolled a nearly identical proportion of patients with extensive disease. 

The researchers conclude that the primary reason for this extended survival compared to previous studies is the life-prolonging additional treatments patients received after they completed the S1216 trial. Some 77 percent of control arm patients whose cancer progressed went on to get additional life-prolonging treatment after finishing the trial therapy, compared to 61 percent in the orteronel arm.

“We are seeing the benefit of the advancements made in advanced  prostate cancer therapy in the last decade, resulting in unprecedented improvements in survival of men with advanced prostate cancer in general, which is great news for our patients,” said study lead author Neeraj Agarwal, MD, a SWOG investigator with the Huntsman Cancer Institute at the University of Utah.

In setting the measure of success for the trial as an improvement in OS of at least 33 percent, the S1216 study team had worked from the assumption that median control arm OS would be 54 months, a figure that built on the SWOG-9346 results and added time to account for the anticipated impact of new drugs then being reviewed for approval. Because the actual median control arm OS exceeded this assumption by 16 months, the results did not meet the threshold for S1216 to be considered a positive trial.

Men on the orteronel arm also had significantly improved median progression-free survival (47.6 months versus 23.0 months) and prostate-specific antigen (PSA) response rates measured at seven months after the start of treatment (complete-, partial-, and no-response rates of 58, 22, and 19 percent versus 44, 31, and 25 percent); these were secondary endpoints in the trial.
 

Study S1216 was supported by the NCI, part of the National Institutes of Health (NIH), led by SWOG, and conducted by the NIH-funded National Clinical Trials Network (NCTN).

The trial was funded by the NIH/NCI through grants CA180888, CA180819, CA180820, and CA180821, and in part by Millennium Pharmaceuticals, Inc. (Takeda Pharmaceutical Company LTD).

In addition to Agarwal, the S1616 study team included Catherine M. Tangen, DrPH, of the SWOG Statistics and Data Management Center; Maha H.A. Hussain, MD, of the Northwestern University Robert H. Lurie Comprehensive Cancer Center; Shilpa Gupta, MD, of the Cleveland Clinic Taussig Cancer Institute; Melissa Plets, MS, of the SWOG Statistics and Data Management Center; Primo N. Lara, MD, of the UC Davis Comprehensive Cancer Center; Andrea L. Harzstark, MD, of Kaiser Permanente–Oakland; Przemyslaw W. Twardowski, MD, of the John Wayne Cancer Institute; Channing J. Paller, MD, of the Johns Hopkins University School of Medicine; Dylan Zylla, MD, of the Metro Minnesota CCRC/Park Nicollet Clinic; Matthew R. Zibelman, MD, of the Fox Chase Cancer Center; Ellis Levine, MD, of the Roswell Park Comprehensive Cancer Center; Bruce J. Roth, MD, of the Washington University School of Medicine; Amir Goldkorn, MD, of the USC Norris Comprehensive Cancer Center; Daniel A. Vaena, MD, of the University of Iowa and the West Cancer Center; Manish Kohli, MD, of the Huntsman Cancer Institute at the University of Utah and the Mayo Clinic at Rochester; Tony Crispino, of the UsTOO Prostate Cancer Support and Education Las Vegas Chapter; Nicholas J. Vogelzang, MD, of the Comprehensive Cancer Centers of Nevada; Ian M. Thompson Jr, MD, of the CHRISTUS Santa Rosa Health System; and David I. Quinn, MD, of the USC Norris Comprehensive Cancer Center.

Reference: Agarwal N et al. "Orteronel for Metastatic Hormone-Sensitive Prostate Cancer: A Multicenter, Randomized, Open-Label Phase III Trial (SWOG-1216)," DOI: 10.1200/JCO.21.02517 Journal of Clinical Oncology. Published online April 21, 2022. https://ascopubs.org/doi/abs/10.1200/JCO.21.02517 
 

SWOG Cancer Research Network is part of the National Cancer Institute's National Clinical Trials Network and the NCI Community Oncology Research Program and is part of the oldest and largest publicly funded cancer research network in the nation. SWOG has nearly 12,000 members in 47 states and nine foreign countries who design and conduct clinical trials to improve the lives of people with cancer. SWOG trials have led to the approval of 14 cancer drugs, changed more than 100 standards of cancer care, and saved more than 3 million years of human life. Learn more at swog.org, and follow us on Twitter at @SWOG.