Trastuzumab Deruxtecan in HER2-Low Advanced Breast Cancer | NEJM

Summary

This phase 3 study investigates the efficacy of trastuzumab deruxtecan in patients with HER2 low metastatic breast cancer. Involving 557 participants, the trial demonstrated that trastuzumab deruxtecan significantly improved median progression-free survival to 10.1 months, compared to 5.4 months with standard chemotherapy. Overall survival rates also showed marked improvement. While adverse events, particularly neutropenia, were common, 12% of patients experienced drug-related interstitial lung disease, mostly mild. The findings suggest trastuzumab deruxtecan offers substantial benefits for this patient population, highlighting its potential as a key treatment option.

Takeaways

• 😀 A significant proportion of HER2-negative metastatic breast cancers are categorized as HER2 low, with low levels of HER2 expression.
• 😀 Current HER2-directed therapies are not effective for patients with low HER2 expression.
• 😀 A new study evaluated the efficacy and safety of trastuzumab deruxtecan in patients with previously treated HER2 low metastatic breast cancer.
• 😀 The study was a phase 3 open-label randomized trial involving 557 patients.
• 😀 Patients were classified based on a HER2 score of 1+ or 2+ without gene amplification.
• 😀 Participants were assigned to receive trastuzumab deruxtecan or a physician's choice of chemotherapy in a 2:1 ratio.
• 😀 The primary endpoint, median progression-free survival for hormone receptor-positive cancer, was significantly longer with trastuzumab deruxtecan (10.1 months) compared to chemotherapy (5.4 months).
• 😀 Overall survival rates in hormone receptor-positive patients improved significantly with trastuzumab deruxtecan.
• 😀 Common adverse events included grade 3 or higher neutropenia in both treatment groups.
• 😀 Drug-related interstitial lung disease or pneumonitis occurred in 12% of trastuzumab deruxtecan patients, most presenting as mild or moderate illness.

Q & A

What type of breast cancer is the study focused on?

The study focuses on HER2 low metastatic breast cancer.

What defines HER2 low expression in this context?

HER2 low expression is defined as a score of 1+ on immunohistochemical analysis or 2+ with no gene amplification.

What was the primary treatment being evaluated in the study?

The primary treatment evaluated was trastuzumab deruxtecan.

How many patients participated in the trial?

A total of 557 patients participated in the trial.

What was the median progression-free survival for patients treated with trastuzumab deruxtecan?

The median progression-free survival for those treated with trastuzumab deruxtecan was 10.1 months.

How did the progression-free survival compare with the physician's choice of chemotherapy?

The progression-free survival with chemotherapy was 5.4 months, significantly lower than with trastuzumab deruxtecan.

What were the key secondary endpoints measured in the study?

Key secondary endpoints included overall survival in hormone receptor positive patients and progression-free survival in all patients.

What adverse events were noted in the study?

Grade three or higher adverse events, particularly neutropenia, were noted, along with 12% of patients experiencing drug-related interstitial lung disease.

What conclusion did the authors reach regarding trastuzumab deruxtecan?

The authors concluded that trastuzumab deruxtecan significantly improved progression-free and overall survival in patients with previously treated HER2 low metastatic breast cancer.

Where can full trial results be found?

Full trial results are available at nejm.org.