Personalized treatment for patients with ovarian cancer is an evolving area of clinical research impacting current practice patterns. Several studies presented at the recent 2025 ASCO Annual Meeting consider new treatments and treatment combinations for ovarian cancer based on patient and tumor characteristics.

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Following these presentations, featured expert Kathleen N. Moore, MD, MS, FASCO, was interviewed by Conference Reporter Medical Director Lauren Weinand, MD. Clinical perspectives from Dr Moore on these findings are presented here.

Progress in outcomes for patients with advanced ovarian cancer is of high priority. Despite initial responses to platinum-based therapy and surgical cytoreduction, recurrences are common, with approximately 80% of patients experiencing disease recurrence within 3 years of diagnosis. Once recurred, there is an increasing armamentarium of efficacious medications at our disposal, but cure is no longer a possibility.

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Two studies presented at ASCO 2025 sought to improve survival with innovation in frontline therapy. The TRUST study (also known as ENGOT ov33/AGO‐OVAR OP7) by Sven Mahner, MD, evaluated the quality and timing of surgical intervention in the frontline setting (abstract LBA5500). This was an international study trying to, once and for all, evaluate the role and timing of surgery for frontline management in patients with advanced ovarian cancer. It has been very controversial for many years whether patients should undergo primary cytoreduction, which can be very complex, vs chemotherapy first and then interval cytoreduction, which tends to be a safer surgery, complication wise. The TRUST study found that, in expert centers with proven surgical quality, primary cytoreduction surgery followed by chemotherapy did not improve overall survival (OS) compared with neoadjuvant chemotherapy followed by interval cytoreductive surgery in patients with stage III or IV advanced ovarian cancer. This study answers criticisms of prior studies regarding surgical quality, and the primary end point of OS was not met. However, the prespecified subset analysis in stage III tumors and in those tumors with complete resection supports the consideration of primary cytoreductive surgery in patients who are fit for surgery, although there should still be individualization of therapy for patients.

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Also at ASCO 2025 was the FIRST trial (also known as ENGOT-OV44) presented by Anne-Claire Hardy-Bessard, MD, evaluating the combination of dostarlimab and niraparib following platinum-based chemotherapy as first-line treatment for advanced nonmucinous epithelial ovarian cancer (abstract LBA5506). We saw a statistically significant improvement in progression-free survival with the combination compared with standard platinum-based therapy, but the clinical benefit was modest, with only a 15% reduction in the progression rate. This was statistically significant given the size of the trial but does not translate into clinical relevance for ICIs in this treatment setting. No OS advantage was seen.

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In the recurrent ovarian cancer setting, mirvetuximab soravtansine is a folate receptor alpha (FRα)–targeting ADC that is being tested in maintenance therapy. It is US Food and Drug Administration (FDA) approved for platinum-resistant ovarian cancer with high FRα expression, defined as at least 75% of cells having at least 2+ staining intensity. This FDA approval is based on improvements in progression-free survival and OS, and mirvetuximab soravtansine is moving up in the lines of therapy. The ongoing GLORIOSA study is looking at maintenance with mirvetuximab soravtansine plus bevacizumab vs bevacizumab alone in FRα-high platinum-sensitive ovarian cancer. GOG-3103 (also known as MK-2870-022/TroFuse-022/ENGOT-ov84) is similar to GLORIOSA, except it is not biomarker gated. It is a phase 3 randomized trial looking at the efficacy and safety of sacituzumab tirumotecan maintenance treatment with or without bevacizumab vs standard of care after second-line, platinum-based doublet chemotherapy in patients with platinum-sensitive recurrent ovarian cancer. It is really an ADC world right now.

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At ASCO 2025, we saw a trial-in-progress presentation for rinatabart sesutecan (Rina-S), which is an ADC that targets FRα and delivers a TOP1 inhibitor directly to cancer cells. GOG-3107 (also known as RAINFOL-OV2) by Angeles Alvarez Secord, MD, MHSc, is a phase 3, randomized, open-label study of Rina-S vs investigator’s choice of chemotherapy in patients with platinum-resistant ovarian cancer (abstract TPS5627). This study is not limited to FRα-high cases. So far, researchers have not presented any data suggesting that the response rate is more or less effective based on the level of biomarker. In data presented to date, the objective response rate is 55.6% among patients treated at the recommended phase 2 dose of 120 mg/m². This phase 3 study will be important, as it may bring a second ADC into the platinum-resistant space with the same target but different payloads, which will make understanding whether sequencing is important a high priority. Additional ADC studies, including the ongoing phase 2/3 study of raludotatug deruxtecan, an ADC targeting CDH6, presented at ASCO 2025 by Laurence Albiges, MD, PhD, are helping to bring active agents to patients with advanced or metastatic ovarian cancer and raise questions about how best to select and sequence these new treatment options (abstract TPS3158).