Trastuzumab duocarmazine could be ‘a new option’ for HER2-positive metastatic breast cancer
medwireNews: Previously treated patients with HER2-positive metastatic breast cancer derive a significant progression-free survival (PFS) benefit from the novel HER2-targeted antibody–drug conjugate trastuzumab duocarmazine relative to standard treatment, shows the TULIP trial.
Cristina Saura Manich (Hospital Universitari Vall d’Hebron, Barcelona, Spain) presented results of the phase 3 trial at the ESMO Congress 2021, reporting on 437 patients who had received prior trastuzumab emtansine (T-DM1) or at least two other treatments for metastatic disease.
PFS, as assessed by central review, was significantly longer among the 291 patients who were randomly assigned to receive trastuzumab duocarmazine (also known as SYD985) at a dose of 1.2 mg/kg every 3 weeks than the 146 given physicians’ choice of chemotherapy, at 7.0 versus 4.9 months and a hazard ratio for progression or death of 0.64.
Median overall survival was 20.4 months with trastuzumab duocarmazine and 16.3 months with chemotherapy, but the between-group difference was not statistically significant at this timepoint, said Manich.
The overall response rate was similar between the trastuzumab duocarmazine and chemotherapy groups, at 27.8% versus 29.5%, but the clinical benefit rate was higher with the antibody–drug conjugate, at 38.5% versus 32.2%.
In addition, health-related quality of life, evaluated using the EORTC QLQ-C30 questionnaire, was not worse with trastuzumab duocarmazine than with chemotherapy.
Overall, treatment-emergent adverse events of grade 3 or higher were reported in 52.8% and 48.2% of the trastuzumab duocarmazine and chemotherapy arms, respectively. The most common events of this severity in the trastuzumab duocarmazine group were keratitis (12.2 vs 0.0%), conjunctivitis (5.6 vs 0.0%), neutropenia (4.9 vs 18.2%), dry eye (4.2 vs 0.0%), fatigue (3.1 vs 1.5%), and pneumonitis (2.1 vs 0.0%).
Manich pointed out that 21.2% of patients taking trastuzumab duocarmazine had grade 3 or higher ocular toxicity, which led to treatment discontinuation in 20.8% of patients and dose modifications in 22.9%. An additional 2.4% of patients developed interstitial lung disease or pneumonitis of this grade, which was associated with discontinuations and modifications in a corresponding 5.2% and 2.1%.
There were four treatment-related deaths in the trastuzumab duocarmazine group (respiratory failure and pneumonia in one patient each and pneumonitis in two), and two deaths unrelated to treatment (acute respiratory failure and COVID-19 pneumonia).
In light of these data, the investigator believes that trastuzumab duocarmazine “can provide a new treatment option” for previously treated patients with metastatic breast cancer.
Discussant Barbara Pistilli (Gustave Roussy, Villejuif, France) noted that trastuzumab duocarmazine “showed a substantial activity after T-DM1,” but she added that “more granular biomarkers” are needed to identify upfront patients who may benefit from one or other antibody–drug conjugate.
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