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.