The Top 5 Gynecologic Cancer Advancements in 2025

2025 was a pivotal year for gynecologic oncology, marked by significant clinical breakthroughs that are reshaping the treatment landscape for some of the most challenging cancers. From novel combinations extending survival in tough-to-treat platinum-resistant ovarian cancer to targeted therapies offering dramatic improvements for molecularly defined subgroups, these advances offer new hope.

Here are the top 5 articles from this year following the advancements in gynecologic cancers.

Maintenance Selinexor Extends PFS in TP53 Wild-Type Endometrial Cancer

The phase 3 SIENDO trial revealed that maintenance therapy with oral selinexor (Xpovio) significantly extended PFS in patients with TP53 wild-type advanced or recurrent endometrial cancer.

In this key subgroup, the median PFS for patients receiving selinexor was 28.4 months, a substantial improvement over the 5.2 months for those on placebo (HR, 0.44). The benefit was particularly striking for patients with mismatch repair-proficientTP53 wild-type disease, who achieved a median PFS of 39.5 months. Although treatment-emergent adverse events (AEs), such as nausea and neutropenia, were common, they were generally manageable. These results establishedselinexor maintenance as a highly effective therapeutic option following initial chemotherapy for this patient population.

Novel ADC Generates Responses in Difficult-to-Treat Ovarian Cancer

The phase 2 portion of the REFRαME-O1 trialshowed that the novel antibody-drug conjugate (ADC) luveltamabtazevibulin generated encouraging responses in patients with platinum-resistant ovarian cancer.

In the optimal dosing cohort, the overall response rate (ORR)was 32% and the disease control rate was 96%. This activity was observed across patients with low to high expression of FRα, which is expressed by 80% of high-grade serous carcinomas. The ADC demonstrated a manageable safety profile, with common AEs including arthralgia and neutropenia. These data support the drug's potential as a new treatment option for this challenging patient population.

Pembrolizumab/Lenvatinib Elicits Responses in HGSOC

The combination of pembrolizumab (Keytruda) and lenvatinib (Lenvima) demonstrated promising clinical activity in patients with platinum-resistant high-grade serous ovarian cancer, a difficult-to-treat disease.

Phase 2 trial data showed an ORR 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 the most common treatment-related AEs being manageable grade 3 toxicities. This dual-agent strategy, which combines an anti–PD-1 checkpoint inhibitor with a multikinase inhibitor, provides a novel and active treatment approach for patients who have few options remaining after platinum-based chemotherapy failure.

PARP Inhibitors Show Promising Response and Clinical Benefit in BRCA-Altered Uterine Leiomyosarcoma

A retrospective analysis found that PARP inhibitors (PARPi), including olaparib (Lynparza), yielded encouraging outcomes for patients with BRCA-altered uterine leiomyosarcoma.

The ORR was 46%, and the clinical benefit rate was 62%, with a median PFS of 13.2 months. Notably, patients receiving PARPi combined with immune checkpoint inhibitors achieved a median PFS of 40.9 months, significantly longer than monotherapy. The clinical benefit was predominantly observed in those with BRCA homozygous deletions. The findings suggest that PARPi offers a superior therapeutic option compared to standard non–first-line treatments for this rare, aggressive cancer.

Relacorilant Extends Survival in Platinum-Resistant Ovarian Cancer

The phase 3 ROSELLA trial showed that the combination of relacorilant and nab-paclitaxelsignificantly improved outcomes for patients with platinum-resistant ovarian cancer compared with nab-paclitaxel alone.

The combination met both co-primary endpoints, resulting in a 30% reduction in the risk of disease progression or death (6.5 months vs 5.5 months) and a better median OS (16.0 months vs 11.5 months). Furthermore, relacorilant was well-tolerated, with no new safety signals observed. These results suggest the regimen has the potential to become a new standard of care for this challenging disease.