Dr McCann on the Use of First-Line TROP2-Directed ADCs in Metastatic TNBC

“We have 2 TROP2-directed ADCs that we could use in TNBC in the first-line metastatic setting.”

Kelly Elizabeth McCann, MD, PhD, an associate professor at the University of California San Diego, discussed the emerging clinical significance of using TROP2-directed antibody-drug conjugates (ADCs) for the treatment of patients with metastatic triple-negative breast cancer (TNBC).

McCann detailed the efficacy of 2 therapeutic options, datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) and sacituzumab govitecan-hziy (Trodelvy), both of which have demonstrated effectiveness in the first-line metastatic TNBC setting. She emphasized how the distinguishing toxicity profiles of these agents provide a critical framework for patient-centered treatment selection and practice.

McCann noted that although both drugs are highly effective, the choice of regimen may be influenced by specific patient markers; for instance, sacituzumab govitecan may be administered alongside pembrolizumab (Keytruda) for patients with disease exhibiting PD-L1 positivity. She explained that understanding the nuances between these drugs is essential, as both agents use a similar topoisomerase I inhibitor payload and target the TROP2 antibody, yet they have key differences.

Furthermore, McCann focused on the specific adverse effects associated with each ADC, acknowledging that sacituzumab govitecan is frequently linked to hair loss and myelosuppression. She stressed that managing these hematologic effects often requires supportive care, such as the administration of filgrastim or pegfilgrastim to maintain healthy neutrophil counts. In contrast, she explained that Dato-DXd is uniquely associated with stomatitis (which can be severe enough to necessitate prophylactic steroid mouthwashes), as well as distinct ocular toxicities.

McCann discussed these agents within the context of recent research, noting that differences in clinical trial design—specifically the presence of patient crossover in the phase 3 ASCENT-03 (NCT05382299) and ASCENT-04 trials (NCT05382286) vs the lack of crossover in the phase 3 TROPION-Breast02 trial (NCT05374512)—affect the interpretation of trial data regarding response rates and overall survival. She emphasized a commitment to distinguishing between these drugs in clinical practice through transparent communication with patients regarding the varied toxicity risks and the distinct designs of the supporting trials for each respective agent.