Oncology News Central (ONC)“Can We Just Stop Already?” Major Breast Cancer Study Leads to Challenges

DESTINY-Breast06 Results Expand Treatment Options While Raising Questions About Sequencing and HER2 Testing

The DESTINY-Breast06 trial results, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrate the potential for earlier use of trastuzumab deruxtecan (T-DXd) in hormone receptor–positive, HER2-low, and HER2-ultralow advanced or metastatic breast cancer. However, these findings also introduce new complexities regarding optimal treatment sequencing and HER2 expression testing. Oncologists are now grappling with how to integrate these results into clinical practice while awaiting further data and updated guidelines.

Key Points:

• DESTINY-Breast06 was a global, randomized, open-label phase 3 study comparing T-DXd to investigator’s choice of chemotherapy.
• The study included patients with HR+, HER2-low, and HER2-ultralow advanced or metastatic breast cancer who had not received prior chemotherapy in the advanced/metastatic setting.
• T-DXd significantly improved progression-free survival (PFS) compared to chemotherapy in the HER2-low population (HR 0.6, median PFS 13 months vs. 8 months).
• Results were consistent in the intention-to-treat population and the HER2-ultralow subgroup.
• Grade 3 or higher toxicities occurred in 40% of T-DXd patients vs. 30% with conventional chemotherapy.
• Interstitial lung disease (ILD) of all grades was observed in 11% of T-DXd patients vs. 1% with chemotherapy.
• The study opens the possibility of using T-DXd earlier in treatment, particularly for high-risk patients.
• Questions remain about optimal sequencing of T-DXd in relation to other therapies, especially considering the tolerability of oral alternatives like capecitabine.
• Overall survival data are needed to further inform treatment sequencing decisions.
• The inclusion of HER2-ultralow patients raises questions about HER2 testing and reporting standards.
• Experts express concern about the lack of data on effective treatments following ADC use.
• The potential requirement for specific HER2 testing methods based on the trial could create logistical challenges for healthcare systems.
• Updated guidelines from ASCO and the College of American Pathologists (CAP) are needed to address HER2-ultralow classification and testing.
• Experts emphasize the importance of individualized treatment decisions based on patient factors and disease characteristics.

“We have no data for any therapy that works after ADCs. Nothing that we have available has ever been studied after T-DXd. The earlier I use it, then I have no idea what to use after it, because we can keep moving it up and up and up and up, but I don’t know what to do after. It’s really complicated.”
– Dr. Stephanie Graff, Breast Medical Oncologist at Legorreta Cancer Center at Brown University in Providence, Rhode Island

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