Dr D'Amato on the Implications of Data With Olaparib Plus Temozolomide in Advanced Uterine Leomyosarcoma

"[Although] the study didn’t meet its end point, it doesn't mean the combination isn't effective. It's just might not be better than what we have. However, I would still say that it's a potential treatment option."

Gina Z. D’Amato, MD, a professor of clinical medicine, assistant director of clinical research, medical director of the Nurse Practitioner Oncology Fellowship Program, and medical director of patient education at the Sylvester Comprehensive Cancer Center and the Miller School of Medicine at the University of Miami, shared efficacy results and key takeaways from the phase 2/3 Alliance A092104 trial (NCT05432791), which evaluated olaparib (Lynparza) plus temozolomide (Temodar) in advanced uterine leiomyosarcoma.

Although the combination demonstrated promise in early-phase evaluation, the randomized trial ultimately failed to meet its primary progression-free survival (PFS) end point in the biomarker-unselected population, D'Amato stated.

Results presented at the 2025 ASCO Annual Meeting showed that patients treated with olaparib plus temozolomide (n = 37) had a median PFS of 3.2 months (95% CI, 2.0-7.0) compared with 5.5 months (95% CI, 2.6-10.2) in those who received investigator’s choice of pazopanib (Votrient) or trabectedin (Yondelis; n = 37; stratified HR, 1.16; 95% CI, 0.67-1.99; P = .703). Furthermore, the median overall survival was longer with the investigational regimen at 19.3 months (95% CI, 15.2-not evaluable [NE]) vs 12.9 months (95% CI, 10.4-NE; HR, 0.70; 95% CI, 0.33-1.47), although this finding was not statistically significant. Based on these findings, the trial will be closed for futility on October 1, 2025.

D’Amato noted that the control agents may have overperformed in this population and emphasized that data specific to uterine leiomyosarcoma remain limited for both pazopanib and trabectedin. Furthermore, existing PFS estimates for these agents are extrapolated from broader soft tissue sarcoma populations, complicating statistical assumptions and interpretability, she added.

Despite these negative results, the combination of olaparib/temozolomide may still represent a viable treatment strategy, particularly in real-world practice, and warrants further exploration, D'Amato concluded.