In the phase III TULIP trial reported in the Journal of Clinical Oncology, Turner et al found that the third-generation HER2-targeted antibody-drug conjugate trastuzumab duocarmazine (T-Duo) improved progression-free survival vs physician's choice (PC) of treatment in patients with previously treated advanced or metastatic HER2-positive breast cancer.
Study Details
In the open-label trial, 437 patients from sites in 11 countries across Europe, Asia, and North America were randomly assigned 2:1 between December 2017 and September 2020 to receive T-Duo at 1.2 mg/kg every 3 weeks (n = 291) or PC of treatment (n = 146) from among lapatinib/capecitabine, trastuzumab/capecitabine, trastuzumab/vinorelbine, or trastuzumab/eribulin. Patients experienced disease progression during or after at least two HER2-targeted therapies or after ado-trastuzumab emtansine (T-DM1). A total of 94% of patients had metastatic disease. A median of three prior HER2-targeted therapies had been administered in the metastatic setting. The primary endpoint was progression-free survival on blinded independent central review.
Progression-Free Survival
Median progression-free survival was 7.0 months (95% confidence interval [CI] = 5.4–7.2 months) in the T-Duo group vs 4.9 months (95% CI = 4.0–5.5 months) in the PC group (hazard ratio [HR] = 0.64, 95% CI = 0.49–0.84, P =.002). Benefit with T-Duo was observed across most predefined subgroups, according to the investigators.
KEY POINTS
- In the phase III TULIP trial, trastuzumab duocarmazine significantly improved progression-free survival vs physician's choice of treatment in patients with HER2-positive advanced or metastatic breast cancer.
- Trastuzumab duocarmazine was associated with ocular toxicity that often resulted in discontinuation of treatment.
In the initial analysis, median overall survival was 20.4 months (95% CI = 18.0–23.7 months) in the T-Duo group vs 16.3 months (95% CI = 13.4–22.8 months) in the PC group (HR = 0.83, 95% CI = 0.62–1.09, P = .153). Objective response was observed in 27.8% vs 29.5% of patients, with a median duration of response of 15.1 months vs 4.6 months.
Adverse Events
Grade ≥ 3 adverse events occurred in 52.8% of the T-Duo group vs 48.2% of the PC group; the most common events were keratitis (12.2%), conjunctivitis (5.6%), and neutropenia (4.9%) in the T-Duo group and neutropenia (18.2%), decreased neutrophils (6.6%), and palmar-plantar erythrodysesthesia syndrome (3.6%) in the PC group. Ocular toxicity of any grade in the T-Duo group included keratitis (38.2%), conjunctivitis (38.2%), and dry eye (30.2%). Adverse events led to discontinuation of treatment in 35.4% of the T-Duo group vs 5.8% of the PC group. Ocular toxicity led to discontinuation of treatment in 20.8% vs 0% of patients.
The investigators concluded: “Treatment with T-Duo was manageable, but tolerability was affected by prevalent ocular toxicity, leading to a higher discontinuation rate in the T-Duo arm. T-Duo significantly reduced the risk of progression in patients with advanced HER2-positive breast cancer who have progressed during/after ≥ 2 HER2-targeted therapies or after T-DM1.”
Evelyn van den Tweel, PhD, of Byondis B.V., Nijmegen, the Netherlands, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Byondis B.V. For full disclosures of the study authors, visit ascopubs.org.
