According to The Asco Post, T-DXd (Enhertu) treatment in the neoadjuvant context resulted in an overall response rate of 75% in patients with localized, hormone receptor-positive, HER2-low breast cancer when no anastrozole was administered and 63% when anastrozole was given.
Aditya Bardia, MD, MPH, and colleagues presented findings from the phase II TRIO-US B-12 TALENT study at the 2022 San Antonio Breast Cancer Symposium. “This is the first report of neoadjuvant T-DXd for patients with HR-positive, HER2-low, localized breast cancer,” says Dr. Bardia.
Chemotherapy is a frequent preoperative treatment for individuals with locally advanced, high-risk breast cancer. Dr. Bardia claims that in situations where tumors express the estrogen receptor and the progesterone receptor, the pathological complete response rate after neoadjuvant chemotherapy is less than 5%.
After binding to HER2, T-DXd penetrates cancer cells. When a cytotoxic payload enters a cancer cell, it causes irreversible DNA damage and kills it. The Food and Drug Administration has approved it for treating malignancies that overexpress the HER2 protein, such as metastatic breast cancer in people with low HER2 expression.
This experiment aimed to determine if T-DXd may enhance outcomes in patients with locally advanced, HER2-low breast cancer who were candidates for curative surgery. Professor of Medicine in the Division of Hematology/Oncology at the University of California, Los Angeles, and Medical Director of the Jonsson Comprehensive Cancer Center’s Clinical Research Unit, Dr. Sara Hurvitz stated that T-DXd showed remarkable efficacy in metastatic HER2-low breast cancer.
Drs. Trinh and O’Brien headed the TRIO-US B-12 TALENT phase II clinical research. Bardia, Hurvitz, and colleagues explored T-DXd and T-DXd in combination with the aromatase inhibitor anastrozole as neoadjuvant therapies. By the first data cutoff in October 2022, seventeen patients had finished all eight T-DXd cycles, and sixteen patients had completed all six T-DXd + anastrozole cycles.
Dr. Bardia defined the study’s primary aim as tumor regression without lymph node involvement after surgery. At the time of the first data cutoff, 5% of patients in the monotherapy arm had achieved a PCR, but none of the patients in the combination treatment arm had.
When the data was cut off, 33 patients had completed all neoadjuvant therapy and surgery, seven were awaiting surgery, and thirteen were still on T-DXd. The response-evaluable group of monotherapy patients had a 75% response rate, with 11 partial and one complete response. Ten patients in the combination treatment group exhibited some improvement, and two patients had complete responses, for a 63% total response rate.
The most common treatment-related adverse effects were hypokalemia (low blood potassium levels), diarrhea, neutropenia (low white blood cell count), fatigue (extreme tiredness), headache, vomiting, dehydration, and nausea (feeling sick). One patient was diagnosed with grade 2 interstitial lung disease. However, he healed once the medicine was stopped.
The number of patients and success rate are still preliminary and susceptible to change. Dr. Hurvitz observed that clinical outcomes, such as PCR and overall response rate, are not mature since not all patients had undergone scans or surgery by the time the data cutoff was reached. She predicted that this patient population’s positive tolerability and overall response statistics would spur additional T-DXd research.
T-DXd was effective in patients with HER2-low, HR-positive, locally advanced breast cancer. Dr. Bardia believes this “provides a translational foundation for future study,” such as using combination regimens in the neoadjuvant context to improve clinical outcomes.
