Episode 20: Primary results from the TROPION-Breast01 study on Dato-DXd in HR+/HER2- metastatic breast cancer treatment
Presented by Dr Kevin Punie (GZA Hospitals) and Prof Evandro De Azambuja (Institut Jules Bordet)
In this episode of WND Breast, Dr Kevin Punie from GZA Hospitals and Prof Evandro de Azambuja from Institut Jules Bordet will discuss the use of ADC in the systemic treatment of metastatic breast cancer patients, as examined in the TROPION-Breast01 study.
The study enrolled over 700 HR+/HER2- breast cancer patients who had experienced progression on endocrine therapy and had received one or two prior lines of chemotherapy. They were randomly assigned to either treatment with the Trop2-directed ADC datopotamab deruxtecan (Dato-DXd) or the physician’s choice of chemotherapy.
Despite the short follow-up period of just 10.8 months, the results indicate a noteworthy statistically significant and clinically relevant improvement in PFS for patients treated with Dato-DXd. Additionally, preliminary analysis at the time of data cut-off suggests a trend favouring Dato-DXd treatment in OS, though conclusive data are pending.
Notably, the majority of patients (63%) received first-line chemotherapy, yet the benefits of Dato-DXd remained consistent across patients with varying treatment histories, demonstrating higher ORR compared to chemotherapy. Interestingly, 70-80% of patients received prior treatment with CDK4/6 inhibitors. Dato-DXd treatment emerges as a promising option for heavily pretreated HR+/HER2- metastatic breast cancer patients refractory to chemotherapy.
The TROPION-Breast01 study also highlighted specific side effects associated with Dato-DXd treatment, including an increased incidence of mucositis and dry eyes compared to chemotherapy, albeit with less haematological toxicity. Of particular concern is the development of ILD, necessitating careful monitoring. ILD occurred across all grades in 90 patients in the Dato-DXd group, whereas none were observed in the chemotherapy group. Overall, the safety profile of Dato-DXd was favourable, exhibiting fewer side effects compared to chemotherapy.
The newest generation of ADCs exhibits some traditional chemotherapy-related side effects. The safety analysis of Dato-DXd indicates lower toxicity, which experts attribute to structural disparities among ADCs.
References:
Bardia A. et al. (2023) Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Primary results from the randomised phase III TROPION-Breast01 trial. Annals of Oncology 34 (suppl_2): S1281-S1282.
