The Changing Landscape for HER2+ Advanced Metastatic Breast Cancer - Episode 3

Updated Data From DESTINY-Breast03 in HER2+ MBC


Practice-changing data from the DESTINY-Breast03 trial evaluating trastuzumab deruxtecan as second-line therapy in HER2-positive metastatic breast cancer presented at ESMO 2021.

Giuseppe Curigliano, MD, PhD:Three weeks ago, we had data from the DESTINY-Breast03 trial during the ESMO [European Society for Medical Oncology] meeting. I would like hear your comments on how those data are changing practice. Dr Criscitiello, can you please explain the DESTINY-Breast03 trial?

Carmen Criscitiello, MD, PhD:Yes, as a reminder the DESTINY-Breast01 trial led to the introduction of trastuzumab deruxtecan into the treatment paradigm for patients with metastatic HER2-positive breast cancer. That was a phase 2 study of trastuzumab deruxtecan in heavily pretreated patients who had HER2+ metastatic breast cancer, with an impressive 6 median prior lines of treatment. We have presently seen updated results of that trial, increased duration of survival in follow-up, with confirmed benefit. At the San Antonio Breast Cancer Symposium 2020, we saw the update in median progression-free survival, which was 19.4 months, and at ESMO this year we saw the updated results for the overall survival [OS], with a median OS of 28.4 months. This is very impressive.

The DESTINY-Breast03 trial is even more impressive. That is a randomized phase 3 study comparing efficacy and safety of trastuzumab deruxtecan versus T-DM1 [trastuzumab emtansine] in patients with HER2+ metastatic breast cancer who were previously treated with trastuzumab and a taxane. In this study, the patients were randomized in a 1:1 ratio. The primary end point was progression-free survival by blinded independent central review, while the secondary end points were overall survival, objective response rate, the duration of response, progression-free survival…and safety.

The study randomized 524 patients, and the results presented at the latest ESMO meeting showed an impressive, compelling hazard ratio in progression-free survival of 0.28. That’s amazing, we have never seen…in a clinical trial in breast cancer. With regard to the overall survival, at the interim analysis we saw an encouraging hazard ratio of 0.56, with a P value of 0.007, although it did not cross…for significance. Another important finding is the 12-month overall survival rate, which is 94% with trastuzumab deruxtecan versus 86% with T-DM1. In terms of objective response rate, it was 80% with trastuzumab deruxtecan and 34% with T-DM1. It’s important and quite impressive that with trastuzumab deruxtecan, only 1.1% of patients had progressive disease as best response. This is a truly amazing drug.

Transcript edited for clarity.