Trastuzumab, docetaxel effective in advanced salivary duct carcinoma
Treatment with trastuzumab plus docetaxel yielded encouraging responses among patients with HER2-positive salivary duct carcinoma, according to results from a prospective phase 2 study published in Journal of Clinical Oncology.
The combination also had a manageable safety profile.
“The largest retrospective study of systemic therapy in patients with advanced [salivary duct carcinoma] to date involved 18 patients treated with carboplatin plus paclitaxel and reported an objective response rate of 39%,” Hideaki Takahashi, MD, PhD, of International University of Health and Welfare Mita Hospital, and colleagues wrote. “Therefore, the development of a novel treatment strategy is warranted.”
Salivary duct carcinoma is one of the most aggressive types of salivary gland carcinoma, which accounts for just 0.2% of all cancers and 8% of all head and neck cancers.
The single-center, single-arm, open-label phase 2 study in Japan enrolled 57 patients (median age, 57 years; range, 38-82; 89% men; 100% Asian) with locally advanced (14%) or recurrent or metastatic (86%) HER2-positive salivary duct carcinoma.
Participants received trastuzumab (Herceptin, Genentech) at a starting dose of 8 mg/kg followed by 6 mg/kg every 3 weeks and docetaxel at 70 mg/kg2 IV every 3 weeks for six cycles. The starting dose of docetaxel was reduced to 55 mg/m2 for patients aged 75 years or older. Patients could continue to receive trastuzumab alone or with docetaxel until disease progression, development of unacceptable adverse events or withdrawal of consent.
Researchers assessed tumors every 6 weeks until disease progression, death or 2 years after treatment initiation. After 2 years, tumors were assessed every 3 months.
Overall response rate served as the primary endpoint. Secondary endpoints included clinical benefit rate, PFS, OS and toxicity.
Median follow up was 28 months (range, 3.6-69)
Results showed an overall response rate of 70.2% (95% CI, 56.6-81.6) and a clinical benefit rate of 84.2% (95% CI, 72.1-92.5). Eight patients (14%) achieved complete response, 32 (56.1%) demonstrated a partial response, 14 (24.6%) had stable disease and three (5.3%) had progressive disease.
Median PFS was 8.9 months (95% CI, 7.8-9.9) and median OS was 39.7 months (95% CI, not reached).
The most common adverse events among patients were anemia (91%), decreased white blood cell count (89%) and neutropenia (88%). Other adverse events included grade 4 decreased neutrophil count (60%) and grade 3 febrile neutropenia (14%). No grade 2 or higher adverse events of heart failure or left ventricular ejection fraction decline to less than 50% occurred.
Researchers said the results must be interpreted with caution because the study was nonrandomized and the sample size was not predefined, noting that further investigation is needed to determine the ongoing effect of the treatment regimen on OS.
“Our results provide evidence that clinical benefit is achievable with trastuzumab plus docetaxel therapy in patients with HER2-positive salivary duct carcinoma,” Takahashi and colleagues wrote. “Our findings support the preliminary data from the basket trials in HER2-positive solid tumors, which demonstrated the concept of tissue- or site-agnostic drug approval on the basis of molecular profiling.” – by John DeRosier
Disclosure s : Takahashi reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.