The SWOG S1216 clinical trial is a Phase III randomized trial of mCSPC where the treatment arms are ADT + bicalutamide or ADT plus orteronel. This study opened in 2013 and closed in 2017 with a goal enrolment of 1,186 patients and an actual enrolment of 1,313 patients. The primary endpoint was overall survival. For this analysis, in SWOG S1216, peripheral blood was drawn with informed consent at registration (baseline), and CTCs were enumerated on the FDA-cleared CellSearch platform (Menarini) per standard manufacturer protocol. CTC counts were analyzed centrally for associations with two pre-specified trial intermediate endpoints: 7-month PSA ≤ 0.2 ng/ml vs. 0.2–4.0 vs. > 4.0, (intermediate endpoint for overall survival, OS); and progression-free survival (PFS) < vs. > 2 years. Because overall survival (OS) data have not matured, an analysis was pooled, and equal numbers of samples were analyzed from each treatment arm and outcome measure as stipulated by the Data Safety Monitoring Committee.
From 2014 to 2017, there were 523 baseline samples collected for this study. In the 7-month PSA response analysis (n = 264), CTCs were detected in 38% of men, with a median of four CTCs in those with detectable CTCs. In the PFS analysis (n = 336), CTCs were detected in 37% of men, with a median of three CTCs in those with detectable CTCs. Adjusting for disease burden (minimal vs. extensive) and ADT status (already initiated or not) at the time of CTC measurement, men with undetectable CTCs were 6.1-fold more likely to attain 7-month PSA response ≤ 0.2 (odds ratio [OR] 6.1, 95% confidence interval [CI] 2.1-17.2, p < 0.001) and 3.7-fold more likely to achieve > 2 years PFS (OR 3.7, 95% CI 1.7-8.1, p < 0.001) compared to men with baseline CTCs ≥ 5.
Other cutpoints previously validated in metastatic castration-resistant prostate cancer (mCRPC) studies (CTC < 5 vs. ≥5 and CTCs 0 vs. ≥1) also strongly discriminated 7-month PSA response and PFS with statistical significance in this mCSPC cohort:
- CTCs < 5 vs. ≥ 5
- PSA complete response: OR 5.08, p=0.002
- 2-year PFS: OR 3.16 (95% CI 1.48-6.75)
- CTCs 0 vs. ≥ 1
- PSA complete response: OR 2.94, p=0.002
- 2-year PFS: OR 2.23 (95% CI 1.36-3.64)
Dr. Goldkorn concluded this study of CTC counts in an analysis of data from SWOG S1216 with the following concluding statements:
- CTC count at the start of treatment for mCSPC was highly prognostic of 7-month PSA response (intermediate endpoint for OS) and of PFS at 2 years
- This is the first such strong evidence from a prospective Phase III trial of this magnitude showing the importance of CTC counts as a prognostic factor
- Baseline CTC count may serve as a valuable prognostic marker to discriminate men likely to respond favorably to hormonal therapies from those who may benefit from early alternate interventions
- Additional analyses using the full sample cohort (>800 sample time points) is planned for when SWOG S1216 primary endpoints are reported
Presented by: Amir Goldkorn, MD, Associate Professor of Medicine, Division of Medical Oncology, Department of Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
Co-Authors: Catherine Tangen, Melissa Plets, Gareth Morrison, Alexander Cunha, Tong Xu, Jacek K. Pinski, Sue A. Ingles, Timothy Triche, Gary R. MacVicar, Daniel A. Vaena, Anthony W. Crispino, David James McConkey, Primo Lara, Maha H. A. Hussain, David I. Quinn, Nicholas J. Vogelzang, Ian Murchie Thompson, Neeraj Agarwal, SWOG GU Committee; Division of Medical Oncology, Department of Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA; SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA; Fred Hutchinson Cancer Research Center, Seattle, WA; University of Southern California, Los Angeles, CA; University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA; USC Keck School of Medicine Norris Comprehensive Cancer Center, Los Angeles, CA; USC/Children's Hospital Los Angeles, Los Angeles, CA; Illinois CancerCare PC, Peoria, IL; University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City, IA; UsTOO Las Vegas, Las Vegas, NV; Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD; University of California, Sacramento, CA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL; USC Norris Comprehensive Cancer Center, Los Angeles, CA; Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Christus Santa Rosa Hospital-Medical Center, San Antonio, TX; Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Augusta, Georgia, Twitter: @zklaassen_md, at the 2020 American Society of Clinical Oncology Virtual Annual Meeting (#ASCO20), May 29th-May 31st, 2020