LIBERTAS: A degendered and transgender-inclusive phase 3 study of apalutamide (APA) plus intermittent vs continuous androgen deprivation therapy (ADT) in participants (pts) with metastatic hormone-sensitive prostate cancer (mHSPC).
Authors: Arun Azad, Clark Musto, Shir Netanel, Tian Zhang, Dana E. Rathkopf, Marco Antonio Badillo, Qiang Dong, Alicia K. Morgans, Karie Runcie, Alex Dos Santos, Amitabha Bhaumik, Suneel Mundle, Sharon McCarthy, Angela Mennicke Lopez- Gitlitz, Ashita S. Batavia, Daniel P. Sanchez, Mark A. Wildgust, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2024)

TPS5119 Background: Individuals with mHSPC may experience adverse events and decreased quality of life associated with ADT. LIBERTAS, the first degendered and transgender-inclusive PC study, explores the use of APA + intermittent ADT as an ADT-minimizing approach in pts who achieve prostate-specific antigen (PSA) &lt;0.2 ng/mL after 6 mo of APA + ADT. mHSPC has been studied almost exclusively in cisgender men. With inclusion of transgender pts who may be receiving feminizing gender-affirming care (GAC), reducing ADT must be approached with deliberate care. LIBERTAS uses broad eligibility criteria to allow inclusion of pts under-represented in clinical trials, including Black and African American pts, transgender, nonbinary, and gender-diverse pts and pts with disabilities. Methods: A patient voice exercise was conducted to gather feedback from pts and caregivers on their experiences with mHSPC and on the proposed study design. All gender-specific language was removed. SOGI (sexual orientation and gender identity) data are collected and reported in the United States. Study site staff are offered healthcare-specific sexual and gender minority cultural sensitivity training. This prospective, international, open-label, randomized study is enrolling pts with metastatic PC documented by conventional imaging, ≤3 mo ADT before enrollment (except as part of GAC), and ECOG PS 0/1; pts with ECOG PS 2/3 are eligible if their score is related to stable disabilities (eg, spinal cord injury, blindness) and not to PC/PC therapy. Pts with bilateral orchiectomy are excluded (except as part of GAC). Stratification factors: tumor volume and prior treatment for localized PC. Pts with confirmed PSA &lt;0.2 ng/mL after initial 6-mo treatment with APA 240 mg/d + ADT are randomized 1:1 to APA 240 mg/d + intermittent ADT or APA + continuous ADT. ADT can be restarted until radiographic progression (assessed by conventional imaging) for pts in the intermittent ADT group with new/worsening cancer symptoms, PSA increase to &gt;10 ng/mL (or return to baseline when PSA &lt;10 ng/mL before ADT), or PSA doubling time &lt;6 mo. Outcomes of pts undergoing medical or surgical GAC are evaluated descriptively as a separate cohort. Primary end points: radiographic progression-free survival and hot flash frequency and severity score at 18 mo from randomization. Secondary end points include findings from electronic patient-reported outcomes completed on a mobile device, digital health assessments measuring physical activity and sleep (measured from a wrist-worn device), and neurocognitive function measured using touchscreen-based interactive assays. An independent data monitoring committee will review safety data. ~333 pts will be enrolled over 2 yrs at 86 sites in 9 countries. Clinical trial information: NCT05884398 .