2025 brought several pivotal advances in gynecologic oncology, with clinical trials producing new options for hard-to-treat cancers and molecularly defined subgroups. The year’s most impactful studies extended survival, produced meaningful response rates, and identified targeted approaches that may change practice.
Maintenance selinexor extends PFS in TP53 wild-type endometrial cancer
The phase 3 SIENDO trial found that maintenance oral selinexor significantly prolonged progression-free survival (PFS) in patients with TP53 wild-type advanced or recurrent endometrial cancer. Median PFS was 28.4 months with selinexor versus 5.2 months with placebo (HR 0.44). Patients with mismatch repair–proficient, TP53 wild-type disease experienced a median PFS of 39.5 months. Treatment-emergent adverse events, including nausea and neutropenia, were common but generally manageable. The data support selinexor maintenance after initial chemotherapy in this population.
Novel ADC generates responses in difficult-to-treat ovarian cancer
The phase 2 portion of the REFRαME-O1 trial reported encouraging activity for the antibody–drug conjugate luveltamab–tazevibulin in platinum-resistant ovarian cancer. In the optimal dosing cohort, the overall response rate was 32% and the disease control rate 96%. Activity was seen across low-to-high folate receptor alpha (FRα) expression, a marker present in about 80% of high-grade serous carcinomas. The safety profile was manageable, with arthralgia and neutropenia among the most common adverse events, supporting further development of the agent for this challenging population.
Pembrolizumab plus lenvatinib elicits responses in high-grade serous ovarian cancer
A phase 2 study of pembrolizumab combined with lenvatinib in platinum-resistant high-grade serous ovarian cancer showed an overall response rate of 37.5%, consisting entirely of durable partial responses, with a median duration of response of 4.14 months. The regimen was generally tolerable, with manageable grade 3 toxicities as the most frequent treatment-related adverse events. The combination of an anti–PD-1 inhibitor and a multikinase inhibitor offers a novel therapeutic option for patients after platinum failure.
PARP inhibitors show activity in BRCA-altered uterine leiomyosarcoma
A retrospective analysis indicated that PARP inhibitors, including olaparib, produced promising outcomes in BRCA-altered uterine leiomyosarcoma. The overall response rate was 46%, the clinical benefit rate 62%, and median PFS 13.2 months. Patients receiving PARP inhibitors combined with immune checkpoint inhibitors had a median PFS of 40.9 months, substantially longer than with PARP inhibitor monotherapy. Clinical benefit was concentrated among patients with BRCA homozygous deletions, suggesting PARP inhibition may offer superior benefit over standard non–first-line therapies in this rare, aggressive tumor.
Relacorilant improves survival in platinum-resistant ovarian cancer
The phase 3 ROSELLA trial demonstrated that relacorilant combined with nab-paclitaxel significantly improved outcomes versus nab-paclitaxel alone in platinum-resistant ovarian cancer. The combination reduced the risk of progression or death by 30%, with median PFS of 6.5 months versus 5.5 months, and improved median overall survival to 16.0 months versus 11.5 months. Relacorilant was well tolerated with no new safety signals reported, supporting its potential as a new treatment option in this setting.
These trial results are reshaping treatment options across gynecologic cancers and underscore the value of targeted and combination strategies in improving patient outcomes.
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