In the global phase III TULIP trial in metastatic HER2-positive breast cancer, treatment with the antibody-drug conjugate vic-trastuzumab duocarmazine (SYD985) significantly improved progression-free survival in comparison with standard chemotherapy in previously treated patients, making this a new treatment option for this population, said Cristina Saura Manich, MD, PhD, Head of the Breast Cancer Program at the Vall d’Hebron University Hospital, Barcelona.1 TULIP met its primary endpoint, with a centrally reviewed median progression-free survival of 7.0 months for trastuzumab duocarmazine vs 4.9 months for chemotherapy (hazard ratio [HR] = 0.64; P = .002).
“These preliminary results [with vic-trastuzumab duocarmazine] are supportive to the primary analysis of progression-free survival. Subsequent analysis of overall survival will be planned when the data are more mature.”— Cristina Saura Manich, MD, PhD
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As presented during the European Society for Medical Oncology (ESMO) Congress 2021, TULIP evaluated trastuzumab duocarmazine, a novel HER2-targeting antibody-drug conjugate comprising trastuzumab bound to a linker drug containing duocarmycin. Its active toxin alkylates DNA, and its drug-to-antibody ratio ranges from 2.4 to 2.8.
About the TULIP Trial
The TULIP trial enrolled 437 patients from 11 countries with HER2-positive locally advanced or metastatic breast cancer previously treated with at least two regimens for metastatic disease or with ado-trastuzumab emtansine (T-DM1) in the metastatic setting. Patients were randomly assigned 2:1 to receive trastuzu-mab duocarmazine (1.2 mg/kg every 3 weeks; n = 291) or physician’s choice (n = 146). Options included trastuzumab/capecitabine, lapatinib/capecitabine, trastuzumab/vinorelbine, and trastuzumab/eribulin. The primary endpoint was progression-free survival by blinded central review.
The median age of patients was 56 years, and the median number of prior treatments was four (range, 1–16). More than 87% of patients in either arm received T-DM1 as well as trastuzumab, and approximately 60% per arm received prior pertuzumab. Treatment of stable brain metastases was allowed if finished at least 8 weeks before enrollment.
Centrally reviewed median progression-free survival was 7.0 months for trastuzumab duocarmazine vs 4.9 months for chemotherapy (HR = 0.64; P = .002). By investigator assessment, median progression-free survival was also significantly improved: 6.9 months vs 4.6 months (HR = 0.60; P < .001).
For the secondary endpoint of overall survival, the medians were 20.4 months with trastuzumab duocarmazine and 16.3 months with chemotherapy—a trend that did not meet statistical significance (HR = 0.83; 95% confidence interval = 0.62–1.09; P = .153). No significant differences were observed in objective response rates or health-related quality of life.
“These preliminary results are supportive to the primary analysis of progression-free survival. Subsequent analysis of overall survival will be planned when the data are more mature,” Dr. Manich said.
Safety Profile
Adverse events led to treatment discontinuation in 35.4% of those given trastuzumab duocarmazine and 10.2% of those given chemotherapy; these adverse events were mainly related to eye disorders (20.8%) or respiratory disorders (6.3%).
The most frequently observed adverse events with trastuzumab duocarmazine were conjunctivitis (38.2%), keratitis (38.2%), and fatigue (33.3%). Interstitial lung disease or pneumonitis occurred in 7.6% of patients on the novel drug, which included grade 1 or 2 events in 5.2%. Two grade 5 events occurred in the experimental arm. More than one-third of patients (35.4%) discontinued treatment with trastuzumab duocarmazine due to adverse events, most frequently citing eye disorders and respiratory disorders.
DISCLOSURE: Dr. Saura Manich reported financial relationships with AstraZeneca, Daiichi Sankyo, Eisai, Exact Sciences, Exeter Pharma, F Hoffmann–LaRoche, MediTech, Merck Sharp & Dohme, Novartis, Pfizer, Philips, Pierre Fabre, Sanofi-Aventis, Seagen, and Zymeworks.
REFERENCE
1. Saura Manich C, O’Shaughnessy J, Aftimos PG, et al: Primary outcome of the phase III SYD985.002/TULIP trial comparing [vic-]trastuzumab duocarmazine to physician’s choice treatment in patients with pre-treated HER2-positive locally advanced or metastatic breast cancer. ESMO Congress 2021. Abstract LBA15. Presented September 19, 2021.
