Dr Westin on Outcomes of the SOLAR Trial in RAS-Mutant Gynecological Malignances

Shannon N. Westin, MD, MPH, FACOG, director, Early Drug Development and Phase I trials Department, professor, Department of Gynecologic Oncology and Reproductive Medicine, discusses the outcomes of the phase 1b SOLAR trial (NCT05554328), which examined olaparib (Lynparza) with selumetinib (Koselugo) in patients with RAS-mutant gynecologic malignancies and other solid tumors.

Within the dose-expansion portion of the trial, investigators examined the combination in 4 different expansion groups: endometrial cancer with RAS pathway activations, ovarian cancer with RAS pathway activations, solid tumors with RAS pathway activations, and ovarian cancer that progressed on a prior PARP inhibitor. RAS pathway activations included KRAS, NRAS, HRAS, BRAF, and NF1 LOF mutations.

Findings presented at the 2023 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancershowed that olaparib plus selumetinib elicited varying degrees of efficacy across the 4 cohorts, with the most exciting data emerging the in RAS-mutant ovarian cancer and RAS-mutant endometrial cancer cohorts, Westin explains.

Patients in the RAS mutant ovarian cancer cohort experienced an overall response rate (ORR) of 32%, with all responders achieving a partial response (PR), and a clinical benefit rate of 69%. Additionally, those patients within that cohort who had low grade serous ovarian cancer had an ORR of 44%. In the RAS-mutant endometrial cancer cohort, the ORR was 35%, with all responders experiencing a PR, and 59% of patients achieved clinical benefit. 

Across the RAS-mutant solid tumor cohort and the PARP-resistant cohort, the benefits were not as prevalent, Westin notes. Two patients with lung cancer experienced a PR in the solid tumor cohort, translating to an ORR of 8%, and the clinical benefit rate was 31%. Notably, among patients with lung cancer, approximately half of these patients achieved a clinical benefit, Westin note. In the PARP-resistant group, the ORR was 17%, and the clinical benefit rate was 42%.

The combination of olaparib and selumetinib is being further explored in patients with RAS-mutant ovarian or endometrial cancer in the ongoing phase 2 ComboMATCH trial (NCT05554328).