[vic]- treatment with trastuzumab duocarmazine (SYD985) for patients with pre-treated locally advanced or metastatic HER2-positive breast cancer (MBC) has provided superior progression-free survival (PFS) data compared to chemotherapy chosen by the physician, based on the results of the TULIP trial (NCT03262935) presented at the ESMO 2021 Annual Meeting.1
“([vic]-trastuzumab duocarmazine) may offer a new treatment option for patients with pretreated, locally advanced or HER2 positive metastatic breast cancer, âsaid study author Cristina Saura Manich, MD, PhD, Head of the breast cancer unit of the medical oncology service at Vall d’Hebron University Hospital in Barcelona, ââSpain, while presenting the results.
The TULIP phase III trial involved 437 patients with locally advanced HER2-positive CBM who had at least 2 prior treatments or at least 1 prior 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 chemotherapy at doctor’s choice (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.
âBaseline demographics, disease characteristics, and previous treatments related to breast cancer were similar between treatment groups,â Manich said, explaining that the median number of previous treatments was 4 (range, 1- 16) in the experimental group and 5 in the experimental group. doctor’s choice group. The time from diagnosis of MBC to enrollment in the study 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 under [vic]-trastuzumab duocarmazine compared to 4.9 months (95% CI, 4.0-5.5 months) for chemotherapy chosen by the doctor. The 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 (RR: 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, although there was no statistically significant difference between [vic]-trastuzumab duocarmazine and physician’s choice chemotherapy seen in the study.
âThese preliminary results support the primary analysis of PFS, and subsequent operating system analysis will be scheduled when the data (is) more mature,â Manich said.
[vic]-trastuzumab duocarmazine is an antibody-drug conjugate that targets the HER2 protein and is composed of trastuzumab linked to duocarmycin, a binding agent.
The most common adverse events (AEs) observed 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 treatment, including 5.2% of grade 1-2 events and 2 grade 5 events. More than a third (35.4%) of patients had stopped treatment with [vic]-trastuzumab duocarmazine due to adverse events, most often citing eye (20.8%) or respiratory (6.3%) disorders.
Manich CS, O’Shaughnessy J, Aftimos PG, et al. LBA15 – Main result of the SYD985.002 / TULIP phase III trial comparing [vic-]trastuzumab duocarmazine, the treatment of choice of the physician in patients with previously treated locally advanced or metastatic HER-positive breast cancer. Presented at: ESMO Annual Congress 2021. September 16-21, 2021.