Multicenter phase II trial of trastuzumab and docetaxel for HER2-positive salivary gland cancer

Backgrounds Standard systemic chemotherapy remains unestablished for recurrent or metastatic (RM) salivary gland cancer (SGC) due to its rarity. A single institute phase II trial of trastuzumab and docetaxel previously showed efficacy with human epidermal growth factor receptor 2 (HER2)-positive SGC.Methods We conducted a multicenter, single-arm, open-label phase II trial of trastuzumab and docetaxel for HER2-positive RM SGC. Patients received trastuzumab 6 mg/kg (loading dose 8 mg/kg) and docetaxel 70 mg/m2 every 3 weeks up to eight cycles. The primary endpoint was the objective response rate (ORR) by a blinded independent review committee. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. Forty-eight patients were screened for HER2 status; 23 were HER2-positive.Results Eighteen patients were enrolled, with 16 receiving the protocol treatment. Fourteen patients were diagnosed with salivary duct carcinoma. The ORR was 60.0% (95% confidence interval [CI], 32.3 to 83.7). The median PFS was 8.5 months (95% CI, 6.0 to 12.7), the median OS, 33.8 months (95% CI, 16.9 to not estimable), and the DCR, 93.3% (95% CI, 68.1 to 99.8). The most frequent grade >= 3 treatment-emerged adverse events were neutropenia (100%), leukopenia (93.8%), lymphopenia (18.8%), and febrile neutropenia (12.5%). One treatment-related death occurred (6.3%) due to hypoalbuminemia.Conclusions These results demonstrate the significant efficacy and predictable toxicities of trastuzumab and docetaxel in patients with HER2-positive RM SGC, leading to the simultaneous approval of trastuzumab and HER2 companion diagnostics assay for this setting in Japan. Trastuzumab plus docetaxel showed significant efficacy and manageable toxicity in HER2-positive recurrent/metastatic salivary gland cancer, leading to simultaneous approval in Japan with HER2 companion diagnostics.