(UroToday.com) The 2024 GU ASCO annual meeting included a prostate cancer session featuring trials in progress and a presentation by Dr. Guilhem Roubaud discussing the trial design of DARIUS (AFU-GETUG P15), a randomized, non-comparative, phase II multicenter trial of short-term darolutamide concomitant to radiation therapy for patients with unfavorable intermediate-risk prostate cancer. ADT with external beam radiation therapy is a standard of care for patients with unfavorable intermediate-risk prostate cancer. However, ADT generates side effects with a 30% decrease of quality of life. Enzalutamide and darolutamide combined with ADT offer an overall survival benefit in advanced prostate cancer, and without ADT, enzalutamide avoids most of the deleterious effects associated with ADT.
In a population of patients with intermediate risk prostate cancer, 92% achieved PSA values < 0.1 ng/ml at the end of a treatment with external beam radiation therapy and enzalutamide alone.1 In pre-clinical models treated with darolutamide alone, testosterone level remained normal.2 Additionally, such side effects related to testosterone loss and to peripheral aromatization of testosterone might be decreased with darolutamide alone. Dr. Roubaud and colleagues assume that a combination of darolutamide given 6 months with external beam radiation therapy in the treatment of unfavorable intermediate risk prostate cancer is efficient and safe, without consequences on quality of life.
DARIUS is a national, multi-center, non-comparative randomized phase II prospective study. The primary objective is to assess antitumor activity of darolutamide given 6 months with external beam radiation therapy in patients with unfavorable intermediate risk prostate cancer, using a biological response defined as PSA ≤ 0.1ng/ml, 6 months after randomization. Darolutamide for 6 months + external beam radiation therapy and ADT for 6 months + external beam radiation therapy are offered in experimental and the standard arm, respectively. Randomization for this trial is 2:1:
Regarding the experimental arm, given that enzalutamide used alone achieved a 49% 6-month biological response rate in hormone-sensible prostate cancer patients,3 the association of darolutamide + external beam radiation therapy will be considered useful if it can increase this rate to at least 70%. Using a single-stage design, standard response rate (P0) is 50% and alternative hypothesis P1 is 70% (one-sided 5% type I error rate, 80% power). Following one-stage A’Hern design, 37 and 19 patients are required in the experimental and standard arm, respectively. Adding 10% of non-eligible/assessable patients, the total number is 62.
Inclusion criteria are:
- PS ECOG ≤ 2
- Histological diagnosis of prostate cancer, without metastasis (on pelvic MRI and thoraco-abdomino-pelvic contrast-enhanced CT-Scan and bone scintigraphy)
- With unfavorable intermediate risk prostate cancer diagnosis (NCCN Guidelines): Either (i) Gleason = 7 (4+3) or, (i) ≥ 50% of the core of biopsies positive for adenocarcinoma or, (iii) two or three of the following criteria: PSA value between 10-20 ng/ml, Gleason 7 (3+4) or Gleason 6 + T2b (clinical or radiological)
Patients with T3a extension on MRI can be included if Gleason score is 6 and PSA < 20 ng/mL. Secondary objectives are biochemical progression free survival, MFS, DFS, prostate cancer-specific survival, time to testosterone recovery, safety, quality of life, and bone mineral density. Predictive factors will be investigated using radiomics and DECIPHER. Since February 2023, 31 patients have been included.
Clinical trial information: NCT05346848.
Presented by: Guilhem Roubaud, Department of Medical Oncology, Institut Bergonié, Bordeaux, France
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, January 25th – January 27th, 2024
References:
- Lara PC, Rodriguez-Melcon JI, Palacios-Eito A, et al. Phase II study of ENZAlutamide combined with hypofractionated radiation therapy (ENZART) for localized intermediate risk prostate cancer. Front Oncol. 2022 Jul 14;12:891886.
- Moilanen AM, Riikonen R, Oksala R, et al. Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies. Sci Rep. 2015 Jul 3:5:12007.
- Tombal B, Borre M, Rathenborg P, et al. Enzalutamide monotherapy in hormone-naïve prostate cancer: Primary analysis of an open-label, single-arm, phase 2 study. Lancet Oncol. 2014 May;15(6):592-600.