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T-DM1 Shows Activity in HER2-Amplified Salivary Gland Cancer in Small Patient Sample of NCI-MATCH


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The antibody-drug conjugate ado-trastuzumab emtansine (T-DM1) showed activity in HER2-amplified salivary gland tumors, according to data published by Jhaveri et al in Annals of Oncology.

The publication is for ‘Arm Q,’ which is one of nearly 40 single-arm phase II treatments in the NCI-Molecular Analysis for Therapy Choice (NCI-MATCH or EAY131) trial. NCI-MATCH is being co-led by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) and the National Cancer Institute (NCI).

“We saw that two of the three NCI-MATCH patients with salivary gland tumors had significant tumor shrinkage by at least 30% with T-DM1 treatment, and this benefit lasted,” said lead researcher Komal Jhaveri, MD, FACP, a medical oncologist and early-phase clinical trials specialist at Memorial Sloan Kettering Cancer Center. “The benefit lasted 2 years in the patient with squamous cell cancer of the parotid gland, and 9 months in the case of mucoepidermoid carcinoma of the parotid gland.”

“This is a hint of activity that needs to become the focus of a larger trial,” added Dr. Jhaveri.

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).

Although the results from Arm Q did not meet these criteria, the signal in salivary gland tumors is important.

KEY POINTS

  • Two of the three NCI-MATCH patients with salivary gland tumors had significant tumor shrinkage by at least 30% with T-DM1 treatment.
  • The benefit lasted 2 years in the patient with squamous cell cancer of the parotid gland, and 9 months in the case of mucoepidermoid carcinoma of the parotid gland.
  • In another trial presented at the 2019 ASCO Annual Meeting, 9 of the 10 patients with salivary gland cancers treated with T-DM1 responded either with tumor shrinkage by computed tomography scan or as assessed by positron emission tomography.

Arm Q Methods and Results

Patients received 3.6 mg/kg of T-DM1 intravenously every 3 weeks until toxicity or disease progression.

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 (excluding breast and gastric), all with a HER2 amplification. Seventeen patients (47%) had stable disease, with median duration of 4.6 months, including 8 of 10 patients with ovarian and uterine carcinomas. The 6-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: 7–139). 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.

“NCI-MATCH seeks to determine whether matching certain drugs or drug combinations in adults whose tumors have specific gene abnormalities will effectively treat their cancer, regardless of their cancer type,” said Lyndsay Harris, MD, Associate Director, Cancer Diagnosis Program, NCI, and co-principal investigator of the NCI-MATCH trial. “In certain studies, such as this, we also saw benefit in rare tumor types. Such discoveries could be eligible to move on to larger, more definitive trials.”

Lyndsay Harris, MD

Lyndsay Harris, MD

Keith T. Flaherty, MD

Keith T. Flaherty, MD

More Evidence of T-DM1 Activity in Salivary Gland Cancer

Another recent trial of T-DM1 (not part of the NCI-MATCH trial) reported interim results at the 2019 ASCO Annual Meeting (Abstract 6001). In that trial, 9 of the 10 patients with salivary gland cancers treated with T-DM1 responded either with tumor shrinkage by computed tomography scan or as assessed by positron emission tomography. As a result, that trial has since been expanded to enroll additional patients.

“We are excited about the prospect of this and other upcoming MATCH arms to shed new light on responsive tumor types, as there is far less data available in rare and uncommon disease types from previously conducted trials,” said Keith T. Flaherty, MD, a medical oncologist at Massachusetts General Hospital Cancer Center and ECOG-ACRIN study chair for the overall NCI-MATCH trial. “Salivary cancer is a particularly understudied area and seeing evidence of benefit for a molecularly targeted approach strongly supports further focus on this cancer type.”

Dr. Jhaveri is the corresponding author for the Annals of Oncology article.

Disclosure: For full disclosures of the study authors, visit academic.oup.com/annonc/.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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