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.