Early data from the ongoing, phase 1b/2 DESTINY-Breast07 trial showed promising efficacy with both trastuzumab deruxtecan monotherapy and trastuzumab deruxtecan plus pertuzumab, with safety profiles consistent with the known profiles for both agents, for patients with previously untreated, HER2-positive metastatic breast cancer.

These data will be presented by Fabrice Andre, MD, Gustave Roussy, Villejuif, France, at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. Trastuzumab deruxtecan has already been approved for patients with HER2-positive advanced or metastatic breast cancer who have received prior anti-HER2–based therapy. This report shares results from the interim analysis of the dose-expansion phase of the multicenter, open-label, phase 1b/2 trial, specifically from modules assessing trastuzumab deruxtecan alone, or in combination with pertuzumab.

These modules enrolled patients with HER2-positive metastatic breast cancer who have not received any prior therapy in the metastatic setting. Patients received either 5.4 mg/kg trastuzumab deruxtecan every 3 weeks alone (monotherapy module; n = 75) or in combination with 420 mg (840 mg loading dose) of pertuzumab (combination module; n = 50). The primary end points were safety and tolerability with key secondary end points of objective response rate (ORR), and progression-free survival (PFS).

The median follow-up duration is 19.2 months in the monotherapy module and 20.6 months in the combination module. The most common adverse event was nausea in 10.7% (grade 3 = 4.0%) of patients in the monotherapy module vs 68% (grade 3 = 0%) in the combination module. There were 34.7% (grade 3 = 2.7%) of patients in the monotherapy module who experienced diarrhea vs 60.0% (grade 3 = 6.0%) in the combination module. There were no grade ≥4 nausea or diarrhea events reported. Adjudicated drug-related interstitial lung disease or pneumonitis was reported in 8% of patients in the monotherapy module vs 10% of patients in the combination module, all grade ≤2. There was one non–treatment-related adverse event which led to death in the monotherapy module, due to post-acute COVID-19 syndrome.

The confirmed ORR was 77.3% with trastuzumab deruxtecan alone and 82.0% with trastuzumab deruxtecan plus pertuzumab. The 12-month PFS rates were 77.3% and 89.4%, respectively.

The study authors noted “analyses from the Phase 3 DESTINY-Breast09 clinical trial will provide definitive data” on trastuzumab deruxtecan with or without pertuzumab in the first-line setting for patients with HER2-positive metastatic breast cancer.

Source:

Andre F, Hamilton EP, Loi S, et al. DESTINY-Breast07: Dose-expansion interim analysis of T-DXd monotherapy and T-DXd + pertuzumab in patients with previously untreated HER2+ mBC. Presented at the ASCO Annual Meeting. May 31 – June 4, 2024; Chicago, IL. Abstract #1009