Dr Birrer on the Potential Utility of ADCs in Platinum-Resistant Ovarian Cancer

Michael J. Birrer, MD, PhD, vice chancellor, director, Winthrop P. Rockefeller Cancer Institute, director, Cancer Service Line, University of Arkansas for Medical Sciences, discusses how the expansion of antibody-drug conjugates (ADCs) can address the need for more effective regimens in platinum-resistant ovarian cancer.

Although ADCs have been utilized in cancer treatment for many decades, their expansion into solid tumors like gynecologic cancer is a more recent development, Birrer begins. There is particular interest in utilizing these agents in platinum-resistant ovarian cancer to fulfill the unmet need for more effective, well-tolerated agents in the treatment armamentarium.

One such ADC is mirvetuximab soravtansine-gynx (Elahere), Birrer states. The agent was the first ADC to receive accelerated approval by the FDA on November 14, 2022, for adult patients with folate receptor alpha (FRα)–positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received 1 to 3 prior systemic treatment regimens. This regulatory decision was based on positive objective response rates (ORR) and duration of response data obtained from the pivotal phase 3 SORAYA trial (NCT04296890).

Recently presented data from the confirmatory phase 3 MIRASOL trial (NCT04209855) in this patient population showed that single-agent mirvetuximab soravtansine significantly improved all efficacy end points compared with physicians' choice of chemotherapy, Birrer details. Patients treated with the agent experienced a median OS of 16.46 months, and a median progression-free survival (PFS) of 5.62 months. Conversely, the median OS was 12.75 months, and the median PFS was 3.98 months in the IC chemotherapy arm. Moreover, the ORR difference between both arms was 16.4% in favor of mirvetuximab soravtansine.

Birrer notes that this aligns with consistent efficacy signals seen in the phase 3 FORWARD-1[/GOG 3011 trial (NCT02631876)]. Although this trial ultimately did not meet its primary end points, its findings supported the design of MIRASOL.

The technology utilized to develop ADCs has also substantially improved in the last several years, Birrer continues. Most current and emerging agents are equipped with more efficient linkers and have higher drug-antibody ratios, making them overall more effective, he explains. In the future, these agents could not only provide a viable treatment alternative for patients with platinum-resistant disease, but may begin to replace taxanes, Birrer says. The use of taxanes in this disease space is often associated with toxicity concerns. As ADCs are generally considered more tolerable, they could fulfill this need for less toxic regimens without diminishing patient responses, Birrer concludes.