The antibody-drug conjugate ado-trastuzumab emtansine (T-DM1) showed promising activity in HER2 amplified salivary gland tumors, according to data published in the Annals of Oncology. The NCI-Molecular Analysis for Therapy Choice (NCI-MATCH or EAY131) trial is being co-led by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) and the National Cancer Institute (NCI), part of the National Institutes of Health.
NCI-MATCH evaluated T-DM1 in patients with HER2-amplified tumors, excluding breast and gastric/gastroesophageal junction (GEJ) adenocarcinomas. The primary objective of each arm in NCI-MATCH is to estimate the proportion of patients who had an objective response (OR). Under predefined criteria, an OR rate greater than 16% in a given NCI-MATCH arm would warrant further study of the agent(s).
The publication is for ‘Arm Q,’ which is one of nearly 40 single-arm phase two treatments evaluated in the trial. Patients received T-DM1 at 3.6 mg/kg intravenously every three weeks until toxicity or disease progression. Although the results from Arm Q did not meet the primary objective criteria, the signal in salivary gland tumors is important.
Of the 38 patients enrolled in Arm Q, 36 were included in the efficacy analysis. Overall, this was a heavily pretreated group of patients with multiple unique histologies. Seventeen patients (47%) had stable disease with median duration of 4.6 months, including eight of 10 patients with ovarian and uterine carcinomas. The six-month progression-free survival rate was 23.6%. Common toxicities were fatigue, anemia, fever and thrombocytopenia. However, this arm did not find any new toxicities for T-DM1.
There was a trend for tumor shrinkage with higher levels of gene copy number as determined by the tumor sequencing assay. The median HER2 copy number was 17 (range: seven-139). Notably, the patient with squamous cell cancer of the parotid gland had a HER2 gene copy number of 129 and the patient with mucoepidermoid carcinoma of the parotid gland had a copy number of 21.
Genentech Inc. provided ado-trastuzumab emtansine for Arm Q under a Clinical Trial Participation Agreement between NCI and Genentech.
T-DM1 is a targeted therapy that contains the monoclonal antibody trastuzumab, which binds to the HER2 protein found on some cancer cells. It also contains the cytotoxic drug DM1, which inhibits tumor cell division. Unlike chemotherapy, antibody-drug conjugates like T-DM1 are intended to target and kill tumor cells while sparing healthy cells.