Trastuzumab deruxtecan may offer significant survival benefits for patients with “HER2-low” metastatic breast cancers for which currently available HER2-directed therapies are ineffective, according to findings presented at ASCO 2022.

Delegates reacted positively to results from the DESTINY-Breast04 phase 3 trial that showed the risk of disease progression or death was approximately 50% lower and the risk of death was 36% lower with trastuzumab deruxtecan than with the physician’s choice of chemotherapy, regardless of hormone-receptor status.

The study enrolled 557 patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy. Low expression of HER2 was defined as a score of 1+ on immunohistochemical analysis or as an IHC score of 2+ and negative results on in situ hybridization.

Most of the patients (88.7%) had hormone receptor–positive disease and (11.3%) had hormone receptor–negative disease. Chemotherapy included capecitabine, eribulin, gemcitabine, paclitaxel or nab-paclitaxel.

In findings published simultaneously in the NEJM, the primary endpoint of was progression free survival (PFS) in hormone receptor–positive patients, which was 10.1 months for patients treated with trastuzumab deruxtecan group compared to 5.4 months in the physician’s choice group (hazard ratio for disease progression or death, 0.51; P<0.001),

For overall survival (OS) the results were 23.9 months and 17.5 months, respectively (HR for death, 0.64; P=0.003).

Across all patients, the median PFS was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice group (HR 0.50; P<0.001), and OS was 23.4 months and 16.8 months, respectively (HR for death, 0.64; P=0.001).

Adverse events of grade 3 or higher occurred in 52.6% of the patients who received trastuzumab deruxtecan and 67.4% of those who received the physician’s choice of chemotherapy.

Drug-related interstitial lung disease or pneumonitis occurred in 12.1% of the patients who received trastuzumab deruxtecan; 0.8% had grade 5 events.

Standing ovation 👏👏👏 for results of DESTINY-Breast04. This will change practice for 50% of patients with metastatic breast cancer. This is why we all went into this field. #bcsm #ASCO22 pic.twitter.com/SQg6Oyd5v9

— Eleonora Teplinsky, MD (@drteplinsky) June 5, 2022

The study investigators said the findings offered potential treatment for the heterogeneous population of breast cancer patients with low levels of HER2, including both hormone receptor–positive and hormone receptor–negative breast cancers.

Currently available HER2-directed therapies have not improved clinical outcomes in patients with HER2-low breast cancers, and after progression during primary therapy these patients commonly receive single-agent palliative chemotherapy, they noted.

“In this trial, we found that targeting low levels of HER2 with trastuzumab deruxtecan was a superior therapeutic approach to untargeted chemotherapy in patients with HER2-low metastatic breast cancer,” the study authors said.

“These results have the potential to improve the treatment outcome for more than half of patients historically categorized as having HER2-negative breast cancer,” they concluded.

The study was suppoted by Daiichi Sankyo and AstraZeneca.