According to analyses from the ICARUS-BREAST01 study, the antibody-drug conjugate patritumab deruxtecan (HER3-DXd) showed promising efficacy and acceptable safety among patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer after 2 or more lines of therapy including a CDK4/6 inhibitor.

These data were first presented by Barbara Pistilli, MD, Gustave Roussy, Villejuif, France, and coauthors, at the 2025 Miami Breast Cancer Conference.

This single-arm, investigator-initiated phase 2 trial enrolled 99 patients who had progressed after CDK4/6 inhibition with endocrine therapy and 1 previous chemotherapy for advanced disease, and who had not been exposed to trastuzumab deruxtecan. Patients received 5.6 mg/kg patritumab deruxtecan every 3 weeks. The study’s primary end point was objective response rate (ORR) as assessed by investigators, with key secondary end points including duration or response, progression-free survival (PFS), clinical benefit rate, and safety.

With a median follow-up duration of 15.3 months, the confirmed ORR was 53.5%, with 2.0% of patients achieving a complete response and 51.5% achieving a partial response. There was an additional 37.4% of patients who achieved stable disease, and the overall clinical benefit rate was 62.6%. The duration of response was 8.7 months and the median PFS was 9.4 months.

There were 98.0% of patients who experienced a treatment-related adverse event of any grade, with 50.1% of those as grade ≥3. The most common treatment-related adverse events, reported in ≥ 10% of patients, included fatigue, nausea, diarrhea, alopecia, constipation, vomiting, anorexia, decreased neutrophil count, abdominal pain, stomatitis, and anemia. There was a total of 13 suspected cases of interstitial lung disease, with 7 adjudicated as related to treatment with patritumab deruxtecan. Of those cases, 2 resulted in treatment discontinuation. Overall, treatment-emergent adverse events led to dose interruption in 26.3% of patients, dose reduction in 20.2%, and treatment discontinuation in 11.1%. There was 1 death on study, due to massive pleural effusion and not determined to be related to the study treatment.

According to the study authors, “The efficacy and safety profile of HER3-DXd makes this [antibody-drug conjugate] an optimal candidate for further, larger trials in patients with hormone receptor-positive, HER2-negative advanced breast cancer after failure of CDK4/6 inhibitors.”

Source:

Rosa K. Patritumab deruxtecan demonstrates meaningful activity in HR+/HER2– advanced breast cancer. OncLive. Published on: March 8, 2025. Accessed on: March 10, 2025. https://www.onclive.com/view/patritumab-deruxtecan-demonstrates-meaningful-activity-in-hr-her2-advanced-breast-cancer