Dr Hinchcliff on the Evolving Role of ADCs in Ovarian Cancer

"The ADCs—across the board—are an incredibly exciting opportunity for targeted therapy."

Emily M. Hinchcliff, MD, MPH, an assistant professor of obstetrics and gynecology (gynecologic oncology) at the Feinberg School of Medicine at Northwestern Medicine, discusses the evolution of antibody-drug conjugates (ADCs) for the treatment of patients with ovarian cancer.

ADCs represent a promising advancement in targeted therapy for patients with ovarian cancer, offering a new treatment strategy with enhanced specificity, Hinchcliff begins. The success of mirvetuximab soravtansine-gynx (Elahere) in the ​phase 3 MIRASOL trial (Study 0416; NCT04209855) marked a significant milestone in ovarian cancer treatment, she says. In ​MIRASOL, patients with folate receptor α (FRα)–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who received the ADC (n = 227) achieved a median overall survival of ​16.5 months (95% CI, 14.5-24.6) vs 12.7 months (95% CI, 10.9-14.4) in those who received ​investigator’s choice of chemotherapy (n = 226; HR, 0.67; 95% CI, 0.50-0.88; P = .0046). Furthermore, the median progression-free survival with the ADC was 5.6 months (95% CI, 4.3-5.9) compared with 4.0 months (95% CI, 2.9-4.5) with chemotherapy (HR, 0.65; 95% CI, 0.52-0.81; P < .0001). These data supported the ​March 2024 regular FDA approval of mirvetuximab soravtansine for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have previously received between 1 and 3 systemic treatment regimens, establishing the ADC as a valuable addition to the current therapeutic paradigm, she explains.

As more ADCs have entered clinical development, key questions have arisen regarding optimal treatment sequencing for patients with FRα expression who may also express other actionable ADC targets, Hinchcliff describes. Determining the optimal order of treatment administration, identifying potential cross-resistance mechanisms, and understanding whether prior exposure to one ADC modulates the efficacy of subsequent therapies remains an area of ongoing investigation, she notes. Additionally, beyond ovarian cancer, ADCs have also demonstrated therapeutic potential in endometrial cancer, signaling the broader efficacy of this class of agents across gynecologic oncology, she concludes.