(UroToday.com) The 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA was host to a prostate cancer trials in progress poster session. Dr. Guillaume Grisay presented EORTC GUCG 2238 De-escalate, a pragmatic trial that aims to revisit intermittent androgen deprivation therapy (ADT) in patients with metastatic hormone-naïve prostate cancer in the era of new androgen receptor pathway inhibitors.
Dr. Grisay noted that, to date, seven trials have established that the addition of an androgen receptor pathway inhibitor (ARPI) to ADT improves survival outcomes for patients with metastatic hormone sensitive prostate cancer (mHSPC). However, treatment intensification comes at the cost of an increased financial and health burden, particularly among those who have a sustained response that, to date, still mandates the continuation of such therapy indefinitely. There has been increased interest over the last several years for identifying potential candidates for treatment de-intensification. The goal of such an approach, termed ‘intermittent maximal androgen blockade’ is to preserve the overall survival benefit, while improving quality of life and reducing resource utilization.
EORTC GUCG 2238 (De-Escalate) is a pragmatic randomized phase 3 trial, where patients achieving a deep PSA response, defined as PSA <0.2 ng/dl following 6 to 12 months of ADT + ARPI, aree randomized 2:1 to:
- Intermittent maximal androgen blockade
- Continuous maximal androgen blockade
The target sample size is 1,600 patients. Patients may have received docetaxel and radiotherapy as part of standard treatment. Recommendations for treatment resumption in the intermittent therapy arm include clinical or radiological progression or PSA increasing to ≥ 50% of diagnostic PSA with a maximum of 5 ng/mL.
The co-primary endpoints are hierarchical:
- The proportion of patients in the intermittent maximal androgen blockade arm that did not restart treatment at one year (H0: not less than 70%)
- Overall survival at 3 years (H0: Intermittent therapy is non-inferior to continuous therapy).
The secondary endpoints include:
- Time to next systemic prostate cancer therapy
- Proportion of patients having received next systemic prostate cancer therapy at 24, 36 and 52 months
- Toxicity with CTCAE v5
- Quality of life with QLQ-C30/PR-25
- IL249 is a new questionnaire developed for De-Escalate based on literature review and discussions with patients/patient representatives, study coordinators, and medical researchers that aims to overcome limitations of QLC-C30 and PR25 for ADT-treated patients
- Health economics parameters (e.g., Incremental cost effectiveness ratio)
The study will use a two-stage consent, as developed by Vickers et al. All patients achieving a deep PSA response will sign a general informed consent form agreeing to data collection. Only patients randomly selected to interrupt their treatment will be given the second informed consent form explaining the purpose of the intermittent arm. If they do not accept, they will remain in the continuous arm. The PRECIS-2 (Pragmatic-Explanatory Continuum Indicator Summary) will be used to evaluate the study as a pragmatic trial.
In summary, EORTC GUCG 2238 (De-Escalate) is a pragmatic phase 3 randomized control trial that will evaluate the feasibility of a de-escalation strategy in men with mHSPC that demonstrate an excellent PSA response after 6 to 12 months of maximal androgen blockade.
Presented by: Guillaume Grisay, MD, Medical Oncologist and Oncogenetics, Centre Hospitalier Jolimont, Universite de Paris, Paris, France
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, January 25th – January 27th, 2024
Related content: The De-Escalate Trial: Intermittently Stopping Prostate Cancer Treatments to Improve Quality of Life - Guillaume Grisay