ADCs

Dr Elisa Agostinetto and Prof Dr Laurence Buisseret, both medical oncologists at the Institut Jules Bordet in Brussels, Belgium, discuss the exciting findings on antibody-drug conjugate (ADC) drugs in breast oncology at ASCO 2024.

The OptiTROP-Breast 01 trial, a randomized phase 3 trial, tested the new ADC sacituzumab-tirumotecan (Sac-TMT). Sacituzumab, an anti-TROP-2 monoclonal antibody, is linked to the cytotoxic agent tirumotecan via a cleavable linker, allowing the release of the cytotoxic agent and creating a bystander effect. The trial showed promising results in pre-treated metastatic triple-negative breast cancer (TNBC), with a significant improvement in PFS of 6.7 months for ADC-treated patients versus 2.5 months for those receiving physician-chosen chemotherapy, along with a notable improvement in overall survival. Regarding safety, the most common grade 3 or higher adverse events were haematological toxicities, including neutropenia, anaemia, and leukopenia. TNBC represents a major unmet clinical need with limited therapeutic options, and these results are particularly relevant for heavily pre-treated populations, where approximately 50% of patients had received three or more prior treatments.

Another significant study was the DESTINY-Breast06 trial, a randomized phase 3 trial testing T-DXd versus physician’s choice chemotherapy in patients with hormone receptor-positive, HER2-low, and HER2-ultralow breast cancer after endocrine therapy. The results showed improved PFS in both HER2-low and HER2-ultralow cohorts, expanding the use of T-DXd to earlier stages of the disease and across a broader patient population, including those with luminal breast cancer. The primary endpoint was the HER2-low population, but the results in the HER2-ultralow cohort were consistent. These findings raise important questions for clinical practice. For instance, T-DXd may be considered for first-line chemotherapy in symptomatic patients needing rapid response, while asymptomatic patients with lower disease burden might benefit from other chemotherapies, reserving T-DXd for second-line treatment. Currently, we lack data on the optimal sequence for these drugs, which future studies will need to address. In practice, discussing options with patients is crucial, considering factors like convenience and toxicity profiles.

Overall, these findings underscore the importance of ADCs in breast cancer treatment, offering new therapeutic avenues for breast cancer patients.