<p>The initial treatment of advanced ovarian cancer is an area of ongoing research, with studies evaluating primary debulking surgery vs neoadjuvant chemotherapy and the optimal maintenance regimens. At the <strong><b>2025 ASCO Annual Meeting</b></strong>, researchers reported the results from some of these trials.</p> <p><br></p> <p><em><i>Following these presentations, featured expert Alexander B. Olawaiye, MD, FRCOG, FACOG, FACS, was interviewed by </i></em>Conference Reporter<em><i> Medical Director Lauren Weinand, MD. Clinical perspectives from Dr Olawaiye on these findings are presented here.</i></em></p>

The initial treatment of advanced ovarian cancer is evolving. Traditionally, we believed that going after ovarian cancer with maximal surgical effort, followed by systemic therapy, would be the best way to treat it. More recently, the EORTC 55971 and CHORUS trials compared primary debulking surgery followed by adjuvant platinum-based chemotherapy with neoadjuvant chemotherapy followed by surgery and adjuvant platinum-based chemotherapy. Both studies reported that neoadjuvant chemotherapy was noninferior to primary debulking surgery. Since these studies were published, the use of neoadjuvant chemotherapy has been increasing. However, one concern with these 2 studies was that the surgical arms may have lacked maximal surgical effort. We have been looking for a study to assess whether it is better to start with maximal surgical effort or neoadjuvant chemotherapy.

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The TRUST trial (also known as ENGOT ov33/AGO-OVAR OP7), which was presented at ASCO 2025 by Sven Mahner, MD, and compared primary debulking surgery with neoadjuvant chemotherapy, vetted surgeons more to ensure maximal surgical effort (abstract LBA5500). The primary end point for TRUST was overall survival (OS), and median OS was 54.3 months in the surgery arm vs 48.3 months in the neoadjuvant chemotherapy arm, which was not statistically significant. When the authors dug deeper into the data, they found that patients who had complete cytoreduction seemed to have much better outcomes. In patients presenting with stage III disease, cytoreductive surgery also looked more effective than neoadjuvant chemotherapy. My interpretation of TRUST is that if you are going to take anyone for primary debulking surgery, it needs to be someone whose tumor you think you can completely resect. Even though the surgery was more intense, patients who received the surgery did not appear to have suffered additional morbidity compared with those in the neoadjuvant chemotherapy arm.

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The phase 3 FIRST/ENGOT-OV44 trial was presented at this year’s ASCO meeting by Anne-Claire Hardy-Bessard, MD, and is evaluating the addition of dostarlimab to platinum-based chemotherapy and niraparib maintenance with or without bevacizumab in patients with advanced ovarian cancer (abstract LBA5506). Enrollment was terminated for a control arm in which patients received neither dostarlimab nor niraparib following the US Food and Drug Administration (FDA) approvals of olaparib and niraparib as maintenance therapy. The trial met its primary end point of progression-free survival with the addition of dostarlimab, but the difference was not clinically significant, at 20.63 vs 19.19 months. FIRST also did not meet the key secondary end point of OS. These results are similar to those from the ATHENA-COMBO trial presented last year at the European Society for Medical Oncology (ESMO) Congress 2024, in which nivolumab was combined with rucaparib and platinum-based chemotherapy. I think that these data should probably put a stop to this strategy of combining immunotherapy with a PARP inhibitor as maintenance therapy.