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09-12-2022 | SABCS 2022 | Conference coverage | News

Encouraging data for neoadjuvant T-DXd in HER2-low early breast cancer

Author: Shreeya Nanda


medwireNews: Trastuzumab deruxtecan (T-DXd) has demonstrated promising efficacy and tolerability in the neoadjuvant treatment of HER2-low, hormone receptor-positive early breast cancer in the TRIO-US B-12 TALENT trial.

“This is the first report of neoadjuvant T-DXd” in this setting, investigator Aditya Bardia (Massachusetts General Hospital, Boston, USA) told the press at the 2022 San Antonio Breast Cancer Symposium in Texas, USA.

“It could provide the groundwork for future studies with antibody-drug conjugates, including T-DXd, for patients with early-stage breast cancer.”

Outlining the rationale for the phase 2 trial, Bardia explained that anthracycline–taxane-based neoadjuvant combination chemotherapy “is often utilized to treat high-risk localized hormone receptor positive breast cancer,” but it is associated with “significant toxicity” and pathologic complete response rates are “low.”

The team therefore investigated the clinical efficacy of T-DXd, which has shown “impressive efficacy” in the metastatic HER2-low setting, in men or pre- or postmenopausal women with resectable HER2-low, hormone receptor-positive, stage II–III breast cancer.

A total of 29 patients (median age, 59 years) received six to eight cycles of T-DXd 5.4 mg/kg every 3 weeks, which led to an objective response in 68% of the 25 evaluable patients. The response was complete in 8% of the patients and partial in 60%.

Bardia and colleagues also assessed the impact of adding anastrozole to the same regimen of T-DXd in a further 29 patients (median age, 55 years), finding that 58% of the 24 evaluable participants achieved an objective response. Once again, 8% had a complete response, while the response was partial in 50%.

The surgical outcomes are pending for 24% of patients who received T-DXd alone and 31% of those who received the antibody–drug conjugate alongside anastrozole, said the presenter.

Among the rest, one patient, who received eight cycles of T-DXd alone, had a pathologic complete response as indicated by a residual cancer burden (RCB) index of 0, while most had an RCB index of II – 50% in the T-DXd alone cohort and 65% in the T-DXd plus anastrozole cohort.

With regard to the safety data, Bardia noted that “the toxicity profile was consistent with what was seen previously with T-DXd.”

He highlighted that “nausea was the number one side effect seen with T-DXd, both as a single agent as well as in combination with anastrozole,” and “the rate of myelosuppression, including neutropenia, was low.”

Five percent of patients across the two groups required a dose reduction due to toxicity and the same proportion discontinued study treatment due to adverse events. One participant had a fatal myocardial infarction after severe gastrointestinal toxicity that was considered possibly related to T-DXd.

Discussing the results, Bardia said that “neoadjuvant trastuzumab deruxtecan demonstrated preliminary evidence of clinical activity in HER2-low, hormone receptor-positive localized breast cancer.”

He continued: “The addition of endocrine therapy to T-DXd did not appear to enhance efficacy, but caution needs to be exerted in deriving strong conclusions given the small numbers.”

The presenter concluded that “the study provides a rich platform for additional translational research to evaluate more sensitive methods of HER2 detection, develop predictive biomarkers, and understand mechanisms of resistance in residual disease which could guide subsequent therapeutic strategies, including combination therapy.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

SABCS 2022; San Antonio, Texas, USA: 6–10 December