[vic]-Trastuzumab Duocarmazine Prolongs PFS in Pretreated, HER2+ mBC

Cristina Saura Manich, MD, PhD

In the TULIP trial, treatment with [vic]-trastuzumab duocarmazine (SYD985) extended progression-free survival (PFS) over standard physician’s choice chemotherapy in patients with pretreated HER2-positive locally advanced or metastatic breast cancer (MBC), according to data presented at the ESMO Congress 2021.

“([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 III TULIP trial (NCT03262935) 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 =0.002) 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 =0.153), 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 brast cancer. Presented at: 2021 ESMO Annual Congress. September 16-21, 2021.}