Good tolerability of datopotamab deruxtecan supports its place in the treatment of HR+/HER2− breast cancer

ESMOBreast24_Jhaveri_LBA2

Komal Jhaveri, US, Giuseppe Curigliano, Italy and Suzette Delaloge, France, during the discussion of the TROPION-Breast01 trial at ESMO Breast Cancer 2024 (Berlin, Germany, 15-17 May)

In the TROPION-Breast01 trial, adverse events of special interest were generally low grade, easily managed and did not compromise scheduled treatment

As reported at ESMO Breast Cancer 2024 (Berlin, 15–17 May), grade ≥3 treatment-related adverse events (TRAEs) were less common with the antibody–drug conjugate (ADC), datopotamab deruxtecan (Dato-DXd), versus investigator’s choice of chemotherapy (21% versus 45%) in 711 patients with previously treated inoperable or metastatic hormone receptor-positive (HR+)/HER2-negative (HER2−) breast cancer (LBA2). At the data cut-off of July 2023, the median treatment duration was longer with Dato-DXd compared with chemotherapy (6.7 months versus 4.1 months). 

ESMOBreast24_TROPION_LBA2

Figure. Safety data from the TROPION-Breast01 study showed that datopotamab deruxtecan had a favourable treatment-related adverse event profile compared with chemotherapy (ESMO Breast Cancer 2024, LBA2)

Given concerns regarding Dato-DXd adverse events of special interest – including stomatitis/oral mucositis and ocular toxicity – daily use of steroid-containing mouthwash was highly recommended and ophthalmological assessment was mandated as a regulatory requirement at screening and every three 21-day cycles. Stomatitis/oral mucositis (56%) and ocular surface events (40%) were generally low-grade (grade 1 in 25% and 32% of all Dato-DXd patients, respectively). Adjudicated drug-related interstitial lung disease (ILD) – another adverse event of special interest – was reported in 3% of patients receiving Dato-DXd and was mainly low grade. Adverse events of special interest generally occurred in the first few cycles of Dato-DXd, with the median onset of stomatitis/oral mucositis at cycle 2, ocular surface events at cycle 3 and ILD at cycle 4. The corresponding median times to resolution were 37, 67 and 28 days, respectively.

Dato-DXd-mediated stomatitis/oral mucositis and ocular surface toxicity were well managed with toxicity management guidelines, resulting in uncommon dose interruptions (1% and 3%, respectively) and discontinuations (0.3% each). For chemotherapy, high-grade neutropenia (grade ≥3 in 31%) was often associated with dose interruptions (17%) and reductions (13%).

ADCs are changing the shape of breast cancer treatment. These additional safety findings from the phase III TROPION-Breast01 trial further support the primary results – presented at the ESMO Congress 2023 (Ann Oncol. 2023;34:Suppl.2;S1264–S1265) – which showed the significant progression-free survival benefits of Dato-DXd over chemotherapy. Mature overall survival results are awaited.

Abstract discussed:

Jhaveri K, et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy (CT) in pretreated, inoperable/metastatic HR+/HER2– breast cancer (BC): Additional safety analysis from TROPION-Breast01. ESMO Breast Cancer 2024, LBA2

Proffered Paper Session 2, 16.05.2024, h. 16:45 – 18:05, Berlin Hall

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.