KEY TAKEAWAYS
- The phase II/III trial aimed to further evaluate olaparib+temozolomide in advanced, pretreated uLMS.
- The primary endpoint was to determine the OS. Secondary endpoints include ORR, duration of response, safety, and patient-reported outcomes.
- Tissue samples will be collected and analyzed for RAD51 foci formation and genomic sequencing. The study opened in January 2023.
Advanced uterine leiomyosarcoma (uLMS) has limited treatment options after initial chemotherapy. Poly ADP-ribose polymerase (PARP) inhibitors may be a promising treatment for HR-deficient uLMS.
Researchers aimed to further evaluate olaparib+temozolomide in advanced, pretreated uLMS pts.
The study included pts with ECOG performance status ≤2, prior progression on ≥ 2 treatment lines, and measurable diseases were randomly assigned 1:1. They either received T 75 mg/m2 orally daily + O 200 mg orally twice daily on days 1-7 in 21-day cycles (Arm 1) or the investigator’s choice of trabectedin 1.5 mg/m2 over 24 hours every 21 days or pazopanib 400-600 mg orally daily (Arm 2). In phase 2, the primary endpoint is PFS, aiming to improve it from 4 to 8 months. This required 70 patients(pts), yielding 90% power with a 1-sided alpha of 0.10. If phase 2 results are positive, phase 3 will follow with enrollment.
The main objective is to assess overall survival (OS), aiming to increase it from 13 to 23 months. This necessitates 165 pts, including 70 from phase 2, and yields 90% power with a 1-sided alpha of 0.025. Secondary objectives include assessing ORR, duration of response, safety, and patient-reported outcomes. Archival tissue will be collected and examined using a RAD51 foci formation assay, and available genomic sequencing results will be obtained. The study began enrolling pts in January 2023.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.TPS11584
Clinical Trial: https://www.clinicaltrials.gov/study/NCT05633381
Kristine Peregrino Lacuna, Sumithra J. Mandrekar, Jacob B. Allred, Stephanie A. Berg, Martee Leigh Hensley, Brian Andrew Van Tine, Suzanne George, Gary K. Schwartz, and Matthew Ingham. DOI: 10.1200/JCO.2023.41.16_suppl.TPS11584 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) TPS11584-TPS11584.
