[vic]-Trastuzumab Duocarmazine Improved Survival For HER2-Positive Metastatic Breast Cancer

Article

Treatment [vic]-trastuzumab duocarmazine improved progression-free survival for patients with pretreated, metastatic HER2-positive breast cancer when compared with physician’s choice chemotherapy.

[vic]-trastuzumab duocarmazine (SYD985) treatment for patients with pretreated HER2-positive locally advanced or metastatic breast cancer (MBC) led to superior progression-free survival (PFS) data over physician’s choice chemotherapy, according to results from the TULIP trial (NCT03262935) presented at the 2021 European Society for Medical Oncology Congress.1

“([vic]-trastuzumab duocarmazine) can provide a new treatment option for patients with pretreated, locally advanced or metastatic HER2-positive breast cancer,” said study author Cristina Saura Manich, MD, PhD, head of the Breast Cancer Unit of the Service of Medical Oncology at Vall d’Hebron University Hospital in Barcelona, Spain, while presenting the findings.

The phase 3 TULIP trial involved 437 patients with HER2-positive locally advanced MBC who underwent 2 or more previous treatments or at least 1 previous treatment with T-DM1. Participants were randomized 2:1 to receive either 1.2 mg/kg of [vic]-trastuzumab duocarmazine every 3 weeks (n = 291) or physician’s choice chemotherapy (n=146), which included lapatinib plus capecitabine; trastuzumab (Herceptin) plus capecitabine; trastuzumab plus vinorelbine; or trastuzumab plus eribulin. Patients continued treatment until progression or unacceptable toxicity.

“The baseline demographics, disease characteristics and prior treatments related to breast cancer were similar between the treatment groups,” Manich said, explaining that the median number of prior treatments was 4 (range, 1-16) in the experimental group and 5 in the physician’s choice group. Time from MBC diagnosis to study enrollment was 4.0 years and 5.0 years in the [vic]-trastuzumab duocarmazine and control arms, respectively.

The most common prior treatments were trastuzumab (89.3% and 86.4% in the [vic]-trastuzumab duocarmazine and physician’s choice arms, respectively), ado-tarstuzumab emtansine (87.6% and 87.5%, respectively), and pertuzumab (Perjeta) (60.8% and 57.5%, respectively).

The primary endpoint of centrally reviewed improved PFS was met, with a centrally reviewed median PFS of 7.0 months (95% CI, 5.4-7.2 months; P = .002) for patients on [vic]-trastuzumab duocarmazine compared with 4.9 months (95% CI, 4.0-5.5 months) for physician’s choice chemotherapy. Investigator-assessed PFS was also better with [vic]-trastuzumab duocarmazine, at 6.9 months (95% CI, 6.0-7.2 months) versus 4.6 months (95% CI, 4.0-5.6 months).

Secondary endpoints included overall survival (OS), which was 20.4 months and 16.3 months, (HR, 0.83; 95% CI, 0.62-1.09; P = .153), which was not statistically significant. Overall response rate (ORR) and health-related quality of life (HRQoL) were also secondary endpoints, though there was no statistically significant difference between [vic]-trastuzumab duocarmazine and physician’s choice chemotherapy observed in the study.

“These preliminary results are supportive to the primary analysis of PFS, and subsequent analysis of the OS will be planned when the data (are) more mature,” Manich said.

[vic]-trastuzumab duocarmazine is an antibody drug conjugate that targets the HER2 protein and is composed of trastuzumab that is bound to duocarmycin, a linker drug.

The most frequently observed adverse events (AEs) for [vic]-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. More than a third (35.4%) of patients discontinued treatment with [vic]-trastuzumab duocarmazine due to adverse events, most frequently citing eye disorders (20.8%) or respiratory disorders (6.3%).

Reference

Manich CS, O’Shaughnessy J, Aftimos PG, et al. LBA15 – 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. Presented at: 2021 ESMO Annual Congress. September 16-21, 2021.

Recent Videos
James Ninia, MD, discussed treatment options for patients with extensive-stage small cell lung cancer undergoing metastasis-directed radiotherapy.
Whole or accelerated partial breast ultra-hypofractionated radiation in older patients with early breast cancer may reduce recurrence with low toxicity.
Ultra-hypofractionated radiation in those 65 years or older with early breast cancer yielded no ipsilateral recurrence after a 10-month follow-up.
The unclear role of hypofractionated radiation in older patients with early breast cancer in prior trials incentivized research for this group.
Patients with HR-positive, HER2-positive breast cancer and high-risk features may derive benefit from ovarian function suppression plus endocrine therapy.
Paolo Tarantino, MD discusses updated breast cancer trial findings presented at ESMO 2024 supporting the use of agents such as T-DXd and ribociclib.
Higher, durable rates of response to frontline therapy are needed to potentially improve long-term survival among patients with non–small cell lung cancer.
Although no responses were observed in 11 patients receiving abemaciclib monotherapy, combination therapies with abemaciclib may offer clinical benefit.
Findings show no difference in overall survival between various treatments for metastatic RCC previously managed with immunotherapy and TKIs.
Related Content