Figure 1: Professors Komal Jhaveri from the USA, Giuseppe Curigliano from Italy, and Suzette Delaloge from France discuss the TROPION-Breast01 study at the 2024 ESMO BC conference (May 15-17, Berlin, Germany).
At the 2024 ESMO BC conference, new data from the TROPION-Breast01 study highlighted that notable adverse events were typically low-grade, manageable, and did not interfere with patients’ expected treatment.
The data presented by Komal Jhaveri at the 2024 ESMO BC conference (Abstract LBA2) from the TROPION-Breast01 study showed that among 711 breast cancer patients with previously treated, inoperable, or metastatic hormone receptor-positive (HR+)/HER2-negative (HER2-) disease, the incidence of grade ≥3 treatment-related adverse events (TRAEs) was lower in the antibody-drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd) group compared to the investigator’s choice chemotherapy group (21% vs. 45%). As of the data cutoff in July 2023, the median duration of treatment was longer in the Dato-DXd group than in the chemotherapy group (6.7 months vs. 4.1 months).
Given the special attention to adverse events associated with Dato-DXd (including stomatitis/mucositis and ocular toxicity), patients are strongly advised to use steroid-containing mouthwash daily and undergo ophthalmological evaluations at enrollment and every 21-day treatment cycle. Stomatitis/mucositis (56%) and ocular surface events (40%) were generally low-grade (Grade 1 stomatitis and ocular surface events occurred in 25% and 32% of all Dato-DXd treated patients, respectively). Reports indicated that 3% of patients treated with Dato-DXd developed drug-related interstitial lung disease (ILD), which was mainly low-grade. These special attention adverse events typically occurred in the first few cycles of Dato-DXd treatment, with median onset times of the 2nd cycle for stomatitis/mucositis, the 3rd week for ocular surface events, and the 4th week for ILD. The median times to resolution were 37, 67, and 28 days, respectively.
According to toxicity management guidelines, Dato-DXd-mediated stomatitis/mucositis and ocular toxicity were well-managed, resulting in rare instances of treatment interruption (1% and 3%, respectively) and discontinuation (0.3% each). In comparison, high-grade neutropenia (≥Grade 3) was common with chemotherapy (31%) and often led to treatment interruptions (17%) and dose reductions (13%).
ADCs are changing the landscape of breast cancer treatment. The additional safety results from the Phase 3 TROPION-Breast01 study further support the primary findings presented at the 2023 ESMO conference (Ann Oncol. 2023;34:sup2; S1264-S1265), showing significant progression-free survival benefits of Dato-DXd over chemotherapy. We are still awaiting mature overall survival results.
