Fabrice Andre, MD, PhD, on Breast Cancer: Interim Analysis From DESTINY-Breast07

HER2 overexpression breast cancer represents around 20% of patients with metastatic breast cancer. The outcome in recent trials is around 50 to 60 months median overall survival with the first-line therapy being Taxane plus Trastuzumab plus Pertuzumab, and this combination provides around 18 months progression-free survival. In this context, there is a need to improve the outcome of these patients. Trastuzumab Deruxtecan is a new drug, it is an antibody-drug conjugate that targets HER2. This drug has shown efficacy in patients who present with HER2 overexpression metastatic breast cancer, previously treated with Taxane Pertuzumab Trastuzumab. In this context, the question is whether giving Trastuzumab Deruxtecan in the first-line setting could improve the outcome of patients. Before moving to the Phase IV / Phase III, it was necessary to run the Phase I / Phase II to explore the safety and preliminary signal of efficacy. In DESTINY-Breast07 Phase I / Phase II, 75 patients were included in the first-line setting to receive Trastuzumab Deruxtecan. 50 patients were included again in the first-line setting to receive Trastuzumab Deruxtecan plus Pertuzumab. What are the results? The response rate was 76% in patients who received Trastuzumab Deruxtecan single agent, and was 84% in the group of patients who received Trastuzumab Deruxtecan plus Pertuzumab. In terms of progression-free survival, it's too early to conclude. Nevertheless, more than 80% of the patients, whether they were treated with Trastuzumab Deruxtecan or T-DXd plus Pertuzumab, more than 80% of the patients had a progression-free survival more than 12 months. Meaning that the disease is controlled for the vast majority of patients for more than 12 months. Then in terms of subgroup, there was no difference of efficacy according to the expression of hormone receptor or whether the disease was recurrent after adjuvant therapy or de novo. In terms of safety, around 10% of patients presented with ILD, which is lung toxicity. Nevertheless, no toxic death was observed. One toxicity that was moderate, but that was increased with Pertuzumab, was diarrhea, but still the number and the percentage are very small. So what can we say about this study? It's a Phase I / Phase II study that tells us that in the first-line setting, T-DXd or T-DXd plus Pertuzumab, provides encouraging preliminary signal of efficacy, and that was the rationale to start a Phase III trial testing this new drug in the first-line setting as compared to the standard of care, and hopefully will improve the outcome of the patients.