Dr Cosgrove on T-DXd Treatment in Ovarian Cancer

Casey M. Cosgrove, MD, gynecologic oncologist, assistant professor, The Ohio State University College of Medicine, The Ohio State University Comprehensive Cancer Center—James Cancer Hospital and Solove Research Institute, discusses treatment with the antibody-drug conjugate (ADC) fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in patients with ovarian cancer.

Treatment with T-DXd has garnered significant attention following its FDA approval for tumor-agnostic use, Cosgrove begins. Within the phase 2 DESTINY-PanTumor02 trial (NCT04482309), the agent showed notable efficacy in managingHER2-positive tumors, particularly in gynecologic cancers, including ovarian, cervical, and endometrial cancers, he reports. Patients with these cancers achieved substantial benefits with T-DXd compared with outcomes seen with other agents in historical data, especially those with HER2 3+ disease; improvements were also observed in those with HER2 expression levels of 2+, Cosgrove says. Oncologists have identified T-DXd as a promising pan-tumor therapeutic option, highlighting its potential for additional research and clinical application, he states.

However, oncologists have contrasted outcomes with T-DXd with those seen with mirvetuximab soravtansine-gynx (Elahere), noting that although the overall safety profile of T-DXd remains favorable compared with traditional therapies, T-DXd is associated with elevated rates of grade 3 or higher severe toxicities, such as interstitial lung disease and cardiac complications, Cosgrove emphasizes. Consequently, increased research is essential to fully understand the safety profiles of T-DXd and mirvetuximab soravtansine as oncologists begin to incorporate these agents into diverse patient populations, he notes.

Another ADC being used in gynecologic oncology is tisotumab vedotin-tftv (Tivdak), which binds to the tissue factor protein, which is highly expressed in cervical cancer cells, Cosgrove continues. Investigators have presented data from the phase 3 innovaTV 301/ENGOT-cx12/GOG-3057 trial (NCT04697628), which demonstrated that tisotumab vedotin significantly improved outcomes compared with investigator’s choice of chemotherapy in patients with metastatic and recurrent cervical cancer. Given the limited therapeutic options for patients with this disease and the generally poor response rates in recurrent cases, the introduction of tisotumab vedotin as a second-line therapy for this patient group is particularly valuable, he says. This development represents a critical advancement in the treatment paradigm for cervical cancer, enhancing the arsenal of therapies available to oncologists, Cosgrove concludes.