Dr Kalinsky on the Potential Role of TROP2-Directed ADCs in IO-Ineligible TNBC

"I would say that TROP2[-directed] ADCs are going to become the frontline standard for our patients with newly metastatic TNBC.”

Kevin Kalinsky, MD, MS, FASCO, a professor and director in the Division of Medical Oncology of the Department of Hematology and Medical Oncology at Emory University School of Medicine, as well as director of the Glenn Family Breast Center at Winship Cancer Institute, discussed the potential role for TROP2-directed antibody-drug conjugates (ADCs) in metastatic triple-negative breast cancer (TNBC).

Kalinsky began by asserting that TROP2-directed ADCs are poised to become the frontline standard of care for newly metastatic disease, regardless of PD-L1 status.

For patients with PD-L1–positive tumors who are eligible for immunotherapy, Kalinsky noted that sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab (Keytruda) could represent a standard of care in the frontline setting, based on data from the phase 3 ASCENT-04 trial (NCT05382286).

For those with PD-L1–negative tumors, the treatment landscape has been expanded by data from 2 major trials: the phase 3 ASCENT-03 study (NCT04827927), which compared sacituzumab govitecan with physician’s choice chemotherapy, and the phase 3 TROPION-Breast02 study (NCT04484142), which evaluated datopotamab deruxtecan-dlnk (Datroway; Dato-DXd) vs physician's choice chemotherapy. Both trials demonstrated significant improvements in progression-free survival and favorable response rates with the ADCs, he reported.

Although Kalinsky notes that both ADCs are effective options for PD-L1–negative disease, they differ in administration and toxicity profiles. Sacituzumab govitecan is administered on a 2 weeks on, 1 week off schedule and is associated with a higher risk of neutropenia. In contrast, Dato-DXd is administered once every 3 weeks, but carries risks for stomatitis and ocular issues. Strategies for managing stomatitis may include the use of oral dexamethasone rinses or sucking on ice cubes during infusion, while patients are encouraged to avoid contact lenses to mitigate ocular risks, Kalinsky explained.

Overall, having 2 TROP2-directed options in TNBC is beneficial, Kalinsky stated. He concluded by noting that clinicians currently lack sufficient data to support sequencing one TROP2 ADC after another.