A safety analysis of the DESTINY-Breast11 study revealed low rates of adjudicated drug-related interstitial lung disease/pneumonitis, left ventricular dysfunction, and neutropenia among patients treated with trastuzumab deruxtecan.

The results, presented at the San Antonio Breast Cancer Symposium (SABCS) 2025, suggested that treatment with trastuzumab deruxtecan, followed by paclitaxel-trastuzumab-pertuzumab (THP), was a safe and manageable option for patients with HER2-positive, high-risk early breast cancer.

DESTINY-Breast11 demonstrated the superiority of trastuzumab deruxtecan, followed by THP, as a neoadjuvant treatment for patients with HER2-positive early breast cancer.

Compared to dose-dense doxorubicin and cyclophosphamide, followed THP, the investigational combination was associated with a statistically significant pathologic complete response improvement.

Initial results showed that trastuzumab deruxtecan provided a superior safety profile compared to dose-dense doxorubicin. At SABCS 2025, researchers presented an analysis designed to report clinically relevant adverse events, including adjudicated drug-related interstitial lung disease/pneumonitis, left ventricular dysfunction, nausea, vomiting, peripheral neuropathy, and neutropenia.

Rates of adjudicated drug-related interstitial lung disease/pneumonitis at all grades were low in all treatment arms, with included trastuzumab deruxtecan alone; trastuzumab deruxtecan followed by THP; and dose-dense doxorubicin followed by THP.

Two patients treated with trastuzumab deruxtecan followed by THP and six patients treated with doxorubicin experienced grade 3 or higher adjudicated drug-related interstitial lung disease/pneumonitis. One patient in each arm experienced a grade 5 case of adjudicated drug-related interstitial lung disease/pneumonitis.

For patients assigned to trastuzumab deruxtecan, low rates of adjudicated drug-related interstitial lung disease/pneumonitis were maintained during the THP phase. Rates were higher during this period of patients assigned to dose-dense doxorubicin.

Among patients with adjudicated interstitial lung disease/pneumonitis, steroid use was common in all three cohorts. The rates of resolution were 57.1%, 71.4%, and 81.3%, respectively.

Compared to trastuzumab deruxtecan alone or in combination with THP, patients assigned to doxorubicin were more likely to experience grade 3 or higher left ventricular dysfunction.

Patients assigned to trastuzumab deruxtecan, with or without THP, were more likely to experience nausea and vomiting than patients assigned to dose-dense doxorubicin. However, during cycle 1 of treatment, these patients were less likely to use any of the three recommended prophylactic antiemetics. The researchers noted that the majority of nausea and vomiting cases were low grade and transient, and the incidence dropped after the first four cycles of treatment.

Patients assigned to doxorubicin had the highest incidence of neutropenia, both at any grade and at grade 3 or higher. Patients assigned to doxorubicin used granulocyte colony-stimulating factor at higher rates than their counterparts assigned to trastuzumab deruxtecan.

Patients assigned to trastuzumab deruxtecan alone had the lowest rates of peripheral neuropathy, compared to treatments containing THP. However, in all cases, the researchers observed mostly low-grade incidences of peripheral neuropathy, with the majority occurring during THP administration.

“[These data] represent a safety profile that is manageable with recommended treatment for patients indicated for trastuzumab deruxtecan, followed by THP.”

─ Giuseppe Curigliano, MD, PhD, University of Milano, Italy, and colleagues

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By Cameron Kelsall

Reference: https://www.abstractsonline.com/pp8/#!/21392/presentation/2300

Disclosures: Some authors declared financial ties to drugmakers. See abstract for details.

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