The combination of trastuzumab (Herceptin) and docetaxel seems to be highly active in patients with unresectable advanced HER2-positive salivary gland carcinoma of the ductal subtype, according to interim data from an open-label, single-arm phase II trial.1 More than two-thirds of patients had a complete or partial tumor response to the combination, and median progression-free survival approached 1 year, investigators reported at the 9th International Conference on Head and Neck Cancer. The main grade 3 and 4 adverse events were a reduction in white blood cell count and neutropenia, each seen in about four-fifths of patients.
While there is no standard or effective treatment modality for metastatic salivary gland cancer, this treatment [trastuzumab plus docetaxel] has a high response rate that is comparable to that with the same combination for breast cancer.— Hideaki Takahashi, MD, PhD
“While there is no standard or effective treatment modality for metastatic salivary gland cancer, this treatment has a high response rate that is comparable to that with the same combination for breast cancer,” commented first author Hideaki Takahashi, MD, PhD, of the Department of Head and Neck Oncology and Surgery, International University of Health and Welfare Mita Hospital, Tokyo, Japan.
“There were no treatment-related deaths, so it is applicable for elderly patients and patients with complications,” he added. “Generally, this treatment is very tolerable, and it is also [delivered] on an outpatient basis, which can help maintain patients’ quality of life.”
The ductal phenotype of salivary gland carcinoma is one of the most aggressive phenotypes, and roughly half of these tumors express HER2, an attractive treatment target, according to Dr. Takahashi.
The investigators enrolled in the trial 45 patients with locally advanced, recurrent or metastatic, unresectable HER2-positive salivary gland carcinoma, with no upper limit on age. All patients were found to have the ductal subtype.
When assessing HER2 status, “we used the same criteria as for breast cancer, which was 3+ by IHC [immunohistochemistry] or more than 2.2 for FISH [fluorescence in situ hybridization],” he said.
The patients were treated with the anti-HER2 monoclonal antibody trastuzumab (loading dose of 8 mg/kg, then 6 mg/kg) and docetaxel (70 mg/m2 for patients younger than age 75, 55 mg/m2 for patients aged 75 years or older) every 3 weeks for at least 6 cycles.
“This treatment is considered feasible,” Dr. Takahashi reported, with 82% of patients completing at least 6 cycles of treatment and a 95% median relative dose intensity for docetaxel.
Results and Toxicity
With a median duration of follow-up of 17.8 months, the overall response rate (the trial’s primary endpoint) was 69%, and the clinical benefit rate (which additionally included stable disease for at least 6 months) was 87%. Median progression-free survival was 11.3 months, and median overall survival was 38.0 months. This efficacy was better than that seen previously with trastuzumab monotherapy and with androgen blockade in this setting, Dr. Takahashi noted.
The main grade 3 and 4 adverse events were a reduction in white blood cell count (seen in 80% of patients), neutropenia (86%), and febrile neutropenia (18%)—a pattern similar to that observed with the regimen in breast cancer. None of the patients developed symptomatic heart failure.
“This was a single-institution study, so we have to validate it by a multicenter phase II study, which is actually ongoing in Japan,” he concluded. ■
Disclosure: Dr. Takahashi reported no potential conflicts of interest.
1. Takahashi H, Masubuchi T, Fushimi C, et al: Trastuzumab and docetaxel for HER2-positive unresectable salivary gland carcinoma: Updated results of a phase II trial. 2016 International Conference on Head and Neck Cancer. Abstract S207. Presented July 18, 2016.
It would be helpful to have an arm of the trial where that chemo [docetaxel] is studied alone, just to make sure the true effect is from the combination and not from the one drug predominantly.— M. Boyd Gillespie, MD, MSCR
“This study is actually surprising to me,...!-->!-->