Trastuzumab Duocarmazine Tried in HER2+ Breast Cancer

TOPLINE:

Trastuzumab duocarmazine (T-Duo) improved progression-free survival to 7.0 months compared with 4.9 months with a physician’s choice in advanced human epidermal growth factor receptor 2–positive (HER2+) breast cancer. However, ocular toxicity was prevalent, leading to higher discontinuation rates in the experimental group.

METHODOLOGY:

• T-Duo is a third-generation HER2-targeted antibody-drug conjugate designed to treat HER2–positive breast cancer. In this TULIP trial, the researchers aimed to evaluate its efficacy and safety in patients with advanced HER2–positive breast cancer who have progressed during or after at least two HER2-targeted therapies.
• A total of 437 patients with unresectable locally advanced or metastatic HER2+ breast cancer were included in the study, and patients were randomly assigned in a 2:1 ratio to receive T-Duo or a physician’s choice of treatment.
• The primary endpoint was progression-free survival, assessed by blinded independent central review. Secondary endpoints included overall survival, objective response rate, and safety.
• Patients received T-Duo 1.2 mg/kg via intravenous infusion every 3 weeks or physician’s choice until disease progression, unacceptable toxicity, or withdrawal of consent.

TAKEAWAY:

• T-Duo significantly improved progression-free survival to 7.0 months compared with 4.9 months with a physician’s choice (P = .002).
• The overall survival was 20.4 months for T-Duo and 16.3 months for the physician’s choice, though the difference was not statistically significant.
• The objective response rate was 27.8% for T-Duo and 29.5% for physician’s choice.
• At least 78.1% of patients who received T-Duo experienced at least one treatment-emergent adverse event categorized as ocular toxicity vs 29.2% of patients in the control group.
• Ocular toxicity events of grade ≥ 3 were reported by 21.2% of patients in the experimental group and none of the patients who received physician’s choice.

IN PRACTICE:

“While T-Duo improved PFS compared to [physician’s] choice, the incremental PFS improvement was more modest than seen with other antibody-drug conjugates. Given the ocular toxicity, it is unlikely that this agent will move into earlier lines of therapy,” wrote Kathy D. Miller, MD, senior deputy editor of the Journal of Clinical Oncology, in the “Relevance” section of the paper.

SOURCE:

The study was led by Nicholas Turner, MD, PhD, The Royal Marsden Hospital and Institute of Cancer Research, London, London, England. It was published online on October 23 in the Journal of Clinical Oncology.

LIMITATIONS:

The study’s limitations included the prevalence of ocular toxicity, which led to a higher discontinuation rate in the T-Duo arm. Additionally, the study did not establish the efficacy of T-Duo in patients previously treated with trastuzumab deruxtecan.

DISCLOSURES:

This study was supported by Byondis B.V. Co-authors Evelyn van den Tweel, Mayke Oesterholt, and Norbert Koper are employees of Byondis. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.