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Sarah Crafton, MD, discusses the potential future of antibody-drug conjugates in patients with ovarian cancer.
Sarah Crafton, MD, gynecologic oncologist, Allegheny Health Network, discusses the potential future of antibody-drug conjugates (ADCs) in patients with ovarian cancer.
ADCs are a unique, novel class of cancer therapy that has had notable success in ovarian cancer, Crafton begins. In 2022, the FDA approved the ADC mirvetuximab soravtansine-gynx (Elahere) for the treatment of patients with folate receptor α (FRα)–positive, platinum-resistant ovarian cancer. The positive data from the pivotal phase 3 SORAYA trial (NCT04296890) indicates that ADCs will continue to be developed to treat patients with this disease, Crafton emphasizes.
HER2-directed ADCs have the potential to change clinical practice for patients with ovarian cancer, Crafton says. Although more ovarian cancer–specific data with ADCs need to be generated, interim results from the phase 2 DESTINY-PanTumor02 trial (NCT04482309), which were presented at the 2023 ASCO Annual Meeting, have sparked excitement across oncology, Crafton explains. This trial evaluated the safety and efficacy of the HER2-directed ADC fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in patients with a variety of HER2-expressing solid tumors.
In the population of patients with ovarian cancer (n = 40), the overall response rate (ORR) was 45.0%, including complete response, partial response, stable disease, and progressive disease rates of 10.0%, 35.0%, 35.0%, and 17.5%, respectively (1 patient was not evaluable). The ORR per independent central review was 42.5%. The 12-week disease control rate was 70.0%, and the median duration of response was 11.3 months (95% CI, 4.1-not evaluable). Although the number of patients with gynecologic cancers enrolled in DESTINY-PanTumor02 was relatively small, these early findings validate the ongoing further research with HER2 as a biomarker in this patient population, Crafton emphasizes.
FRα is another common target for ADCs in ovarian cancer, Crafton notes, adding that additional ovarian cancer clinical trials are investigating TROP2 as another potential target for ADCs in this patient population. Many of the ADCs targeting FRα and TROP2 are still in early development, but they will be important to watch for in the future, Crafton notes.
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