Sep 27

SS 02 - Escalate, De-escalate, or Substitute? Trials Shaping Prostate Cancer Care

107 - Co-Primary Endpoint Analysis for the INTREPId Randomized Trial of Prostate Radiation Therapy with Androgen Deprivation Therapy vs. Darolutamide Monotherapy

03:00pm - 03:10pm ET

Room 205

Presenter(s)

Martin King, MD, PhD - Brigham and Women's Hospital, Boston, MA

M. T. King¹, D. R. Wise², A. Katz³, J. M. Michalski⁴, G. Bubley⁵, S. E. Finkelstein⁶, T. M. Seibert⁷, L. Nordquist⁸, P. Leger⁹, A. Gulati¹⁰, C. Pieczonka⁶, S. Bober¹¹, K. Y. Shin¹², C. Breneman¹³, P. F. Orio III¹⁴, M. Pomerantz¹¹, and P. L. Nguyen¹⁵; ¹Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, ²Department of Medicine, Perlmutter Cancer Center at NYU Langone Medical Center, New York, NY, ³Department of Urology, Perlmutter Cancer Center at New York University Langone Hospital - Long Island, Mineola, NY, ⁴Washington University School of Medicine, St. Louis, MO, ⁵Beth Israel Deaconess Medical Center, Boston, MA, ⁶Associated Medical Professionals of NY / US Urology Partners, Syracuse, NY, ⁷Research Service, VA San Diego Healthcare System, San Diego, CA, ⁸Genitourinary Research Network, Omaha, NE, ⁹Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, ¹⁰Stamford Hospital, Stamford, CT, ¹¹Dana-Farber Cancer Institute, Boston, MA, ¹²Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, ¹³Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, United States, ¹⁴Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, ¹⁵Mass General Brigham Cancer Institute, Boston, MA

Purpose/Objective(s):

For intermediate risk prostate cancer, the addition of 6-months of androgen deprivation therapy (ADT) to dose-escalated external beam radiation therapy (EBRT) reduces the risks of biochemical failure and metastasis. However, ADT has been associated with decreased libido and erectile dysfunction. For the INTREPID randomized trial (NCT04025372), we hypothesized that the androgen receptor pathway inhibitor Darolutamide + EBRT could be used in place of ADT + EBRT for improving erectile quality-of-life without sacrificing oncologic control. Herein, we report the pre-planned co-primary endpoints of erectile function and PSA suppression within the first 6-months from end-of-treatment (EOT).

Materials/Methods:

Patients with intermediate risk prostate cancer and good erectile function, based on the erectile quality question from EPIC 26 (responses 3 or 4), were randomized 1:1 to the control arm (6-months ADT with gonadotropin-hormone releasing agonist plus bicalutamide + EBRT) versus the experimental arm (6-months Darolutamide + EBRT). Patients were stratified by the number of unfavorable intermediate risk factors (0-1 versus 2-3), RT modality (EBRT versus SBRT/combination brachytherapy boost), and age (<65 versus >= 65). The primary endpoint evaluated whether the experimental arm was non-inferior to the control arm with respect to PSA nadir < 0.5 between EOT and EOT + 6 months. Non-inferiority would be established, if the upper bound of two-sided 95% confidence interval (CI) of the observed difference in proportion (control arm minus experimental arm) is less than 9%. The hierarchical endpoint evaluated whether a greater percentage of patients on the experimental arm maintained good erectile function based on the erectile quality question at 3-months from EOT. This endpoint was to be evaluated with a Fisher’s exact test with a two-sided alpha, only if the primary endpoint was positive.

Results:

From 6/2/2020 to 10/16/2024, 234 patients were randomized 1:1 (121 ADT, 113 Darolutamide) across 10 institutions. The percentage of patients with 2-3 unfavorable intermediate risk factors was 39.7% (93/234). The percentage of patients who received IMRT was 41.9% (98/234). The percentage of patients who had a PSA nadir <= 0.5 between EOT and EOT + 6-months was 99.1% (111/112) for the control arm and 90.8% (99/109) for the experimental arm. The difference in proportion was 8.3% and the upper bound of the two-sided 95% confidence interval was 14.4%; non-inferiority was not established. The percentages of patients with good erectile function at 3-months from EOT were 43.6% (44/101) and 71.9% (69/96) for the control and experimental arms, respectively.

Conclusion:

Darolutamide + EBRT did not meet the primary endpoint of non-inferiority for early PSA suppression. Three-year PSA control results will be reported with further follow-up.