Novel conjugate meets primary endpoint

The phase 3 TULIP trial, investigating the novel antibody drug conjugate trastuzumab duocarmazine, met its primary endpoint of extended median progression-free survival (PFS) in HER2-positive breast cancer patients, compared with physician’s choice, in the third-line setting. These results were presented in the second Presidential Symposium.

Trastuzumab duocarmazine is an antibody drug conjugate that targets the HER2 protein with trastuzumab to deliver the cytotoxin duocarmycin after internalisation. Presented by Dr Cristina Saura (Vall d’Hebron Institute of Oncology, Spain), the TULIP trial (NCT03262935) aimed to demonstrate that trastuzumab duocarmazine (1.2 mg/kg every 3 weeks) is superior to physician's choice of treatment in prolonging PFS per blinded independent central review, as its primary endpoint [1].

Eligible patients were randomly assigned 2:1 to receive trastuzumab duocarmazine (n=291) or physician's choice treatment (n=146) until disease progression or unacceptable toxicity. Physician’s choice of treatment included lapatinib plus capecitabine, trastuzumab plus capecitabine, trastuzumab plus vinorelbine, or trastuzumab plus eribulin. This randomised, active-controlled, superiority study in patients with unresectable locally advanced or metastatic HER2-positive breast cancer enrolled patients who had either progression during or after at least 2 HER2-targeting treatment regimens for locally advanced or metastatic disease or progression during or after trastuzumab emtansine (T-DM1) treatment. Key secondary endpoints were overall survival (OS), investigator-assessed PFS, objective response rate, and patient-reported outcomes for health-related quality of life.

The primary endpoint of centrally reviewed improved PFS was met, with a median of 7.0 months (95% CI 5.4–7.2 months) for patients in the trastuzumab duocarmazine arm compared with 4.9 months (95% CI 4.0–5.5 months) for physician’s choice chemotherapy (P=0.002). Likewise, the secondary endpoint of investigator-assessed PFS was also met; patients in the trastuzumab duocarmazine arm had a median PFS of 6.9 months (95% CI 6.0–7.2 months) versus 4.6 months (95% CI 4.0–5.6 months) in the physician’s choice arm.

At the timepoint of this interim analysis, OS was not statistically significant: 20.4 months in the group taking trastuzumab duocarmazine versus 16.3 months in the group following their physician’s choice of therapy (HR 0.83; 95% CI 0.62–1.09; P=0.153). The other key secondary endpoints, objective response rate and health-related quality of life, also showed no statistically significant differences between the 2 arms. Final analyses of these endpoints will be evaluated after the data have matured with follow-up.

Safety signals were manageable, and no cardiotoxicity was observed. The most frequent adverse events for trastuzumab duocarmazine were conjunctivitis (38.2%), keratitis (38.2%), and fatigue (33.3%). Interstitial lung disease/pneumonitis occurred in 7.6% of patients on the drug, including 5.2% grade 1-2 events, and 2 grade 5 events.

1. Saura Manich C, 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 HER-positive locally advanced or metastatic breast cancer. Abstract LBA15, ESMO Congress 2021, 16–21 September.

 

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Posted on 19 November 202129 February 2024