|The following article features coverage from the European Society for Medical Oncology (ESMO) Congress 2021. Click here to read more of Cancer Therapy Advisor’s conference coverage.|
A novel HER2-targeting antibody-drug conjugate showed promise as a treatment option for heavily pretreated advanced or metastatic breast cancer (MBC), according to findings of the TULIP trial presented at the European Society for Medical Oncology (ESMO) Congress 2021.
Trastuzumab duocarmazione (SYD985) is comprised of trastuzumab bound to a linker drug containing duocarmycin. The TULIP trial (ClinicalTrials.gov Identifier: NCT03262935) assessed the efficacy of this novel antibody-drug conjugate in 437 patients with HER2-positive locally advanced or MBC patients with 2 or more previous MBC regimens or previous MBC treatment with trastuzumab emtansine.
Patients from 11 countries were randomly assigned to receive SYD985 at 1.2 mg/kg every 3 weeks (291 patients) or physician’s choice of chemotherapy (146 patients). The median number of prior MBC treatments was between 4 and 5, and the median age of participants was 57 years.
Cristina Saura Manich, MD, PhD, an oncologist at the University Hospital of Vall d’Hebron in Spain, reported the study’s results.
The primary endpoint was progression-free survival (PFS) by blinded central review. Secondary endpoints were investigator-assessed PFS, overall survival (OS), objective response rate (ORR), and health-related quality of life (HRQoL).
The centrally reviewed median PFS was 7 months for SYD985 and 4.9 months for chemotherapy (hazard ratio [HR], 0.64). Investigator-assessed PFS was also significantly improved – 6.9 months vs 4.6 months (HR, 0.60). In the first analysis of OS, the HR was 0.83. “This makes SYD985 statistically superior to physician’s choice chemotherapy,” Dr Manich said.
No significant differences were observed in ORR or HRQoL.
The most frequently reported adverse events in patients in the SYD985 arm were conjunctivitis (38.2%), keratitis (38.2%), and fatigue (33.3%). In the chemotherapy arm, the most frequently reported adverse events were diarrhea (35.8%), nausea (31.4%) and fatigue (29.9%).
Adverse events of special interest included eye toxicity, which was higher in the SYD985 group (78.1%) than in the chemotherapy group (29.2%), and led to discontinuation of treatment in 22.9% of the SYD985 group. For patients in the SYD985 arm, interstitial lung disease (ILD)/pneumonitis was reported for 7.6% of patients (2.4% with grade 3 or higher).
Six deaths occurred in the trial, 4 in the SYD985 group due to respiratory failure, pneumonia and pneumonitis; 2 deaths were not related to treatment.
“Treatment with SYD985 significantly improved PFS in comparison with standard physician’s choice treatment,” Dr Manich concluded. “Ocular toxicity is the most prevalent safety event. ILD/pneumonitis grade 3 or worse was reported in 2.4% of patients. These toxicities have to be carefully monitored and treated appropriately. SYD985 can provide a new treatment option for patients with pretreated, locally advanced or metastatic HER2-positive MBC.”
Disclosures: This research was supported by Byondia B.V. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Manich CS, O’Shaughnessy J, Aftimos PG, et al. Primary outcome of the phase III SYD995.002/TULIP trial comparing [vic] trastuzumab duocarmazine to physician’s choice treatment in patients with pre-treated HER2-positive locally advanced or metastatic breast cancer. Presented at: European Society for Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. Abstract LBA15.