(UroToday.com) The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a prostate, testicular, and penile cancers poster session. Dr. Mamta Parikh presented exploratory analysis of the SWOG S1216 trial evaluating the overall survival (OS) prognostic values of 3- and 7-months serum PSA levels in metastatic hormone sensitive prostate cancer (mHSPC) patients treated with ADT +/- orteronel.
The seven-month PSA level has been established as a prognostic marker for OS in mHSPC patients receiving systemic therapy with ADT +/- docetaxel.1 The objective of this study was to evaluate whether both 3-month and 7-month PSA levels are significantly associated with OS, within the context of the phase 3 S1216 trial.
In brief, SWOG S1216 was a phase III randomized controlled trial of mHSPC patients randomized in a 1:1 fashion to either an LHRH agonist + orteronel versus an LHRH agonist + bicalutamide. This trial, which included 1,279 patients, failed to meet its primary endpoint with no significant differences in OS observed between the two arms (HR: 0.86, 95% CI: 0.72 – 1.02). Of note, median OS in the control arm of LHRH agonist + bicalutamide was 70.2 months,2 which is significantly longer than that observed in the control arms of other trials in this space, likely related in part to the use of an active control (bicalutamide) and the emergence/approval of novel agents in the ≥2nd line setting over more recent years.
This analysis included all patients enrolled in the S1216 trial with available 3- and 7-month PSA levels. PSA responses were defined as follows:
- Complete response (CR): PSA ≤0.2 ng/mL
- Partial response (PR): PSA 0.2 – 4.0 ng/ml
- No response (NR): PSA >4 ng/ml
The association between 3- and 7-month PSA levels with OS outcomes was evaluated using Cox regression modeling adjusted for the following stratification factors: performance status, extent of disease, early versus late start of treatment, and treatment arm.
This analysis included 1,251 evaluable patients for 3-month PSA and 1,231 for 7-month PSA, for a total of 1,279 patients. Median patient age was 67 years, 10% were African American or Black, and 96% had a Zubrod performance status of 0-1. The median PSA at baseline was 29 ng/ml (range: 2 – 6,710 ng/ml).
At 3 months follow-up, a PSA CR was observed in 52% of patients in the combination arm versus 35% patients in the control arm. Similarly, at 7 months, a PSA CR was observed in 61% versus 46% of patients in the intervention and control arms, respectively. As summarized in the table below, a PSA CR at 3 months (HR: 0.34, p<0.001) and 7 months (HR: 0.20, p<0.001) were both significantly associated with improved OS outcomes.
No interaction between treatment arm and PSA response was observed for OS.
Dr. Parikh concluded that 3- and 7-month PSA responses are strong prognostic markers for OS in mHSPC patients receiving systemic therapy. In addition to its utility for counseling patients in the clinical setting, the investigators suggested that 3- and 7-month PSA levels may be used as surrogate endpoints for designing future clinical trials in this disease space.
Presented by: Mamta Parikh, MD, MS, Assistant Professor, Department of Medicine, University of California, Davis, CA
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.References:
- Harshman LC, et al. Seven-Month Prostate-Specific Antigen Is Prognostic in Metastatic Hormone-Sensitive Prostate Cancer Treated With Androgen Deprivation With or Without Docetaxel. J Clin Oncol, 2018;36(4):376-82.
- Agarwal N, et al. Orteronel for Metastatic Hormone-Sensitive Prostate Cancer: A Multicenter, Randomized, Open-Label Phase III Trial (SWOG-1216). J Clin Oncol, 2022;40(28):3301-9.