Phase II Trial of Trastuzumab and Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2–Positive Salivary Duct Carcinoma

Abstract

Purpose Clinical evidence demonstrating the effectiveness of systemic therapy for advanced salivary duct carcinoma (SDC) is lacking because of the disease’s rarity. We assessed the efficacy and toxicity of trastuzumab plus docetaxel in patients with locally advanced and/or recurrent or metastatic human epidermal growth factor receptor 2–positive SDC. Patients and Methods This was a single-center, single-arm, open-label, phase II study in Japan. The patients received trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks. Docetaxel 70 mg/m2 was administrated every 3 weeks. The primary end point was the overall response rate; the secondary end points included the clinical benefit rate, progression-free survival, overall survival, and toxicity. This study is registered with the University Hospital Medical Information Network Clinical Trials Registry (Identification No. UMIN000009437). Results Fifty-seven eligible patients with SDC were enrolled. The overall response rate was 70.2% (95% CI, 56.6% to 81.6%), and the clinical benefit rate was 84.2% (95% CI, 72.1% to 92.5%). Median progression-free and overall survival times were 8.9 months (95% CI, 7.8 to 9.9 months) and 39.7 months (95% CI, not reached), respectively. The most frequent adverse event was anemia (52 patients [91%]), followed by a decreased WBC count (51 patients [89%]) and neutropenia (50 patients [88%]). The most frequently observed grade 4 adverse event was a decreased neutrophil count (34 patients [60%]). Grade 3 febrile neutropenia was reported in eight patients (14%). No grade 2 or greater adverse events of heart failure or left ventricular ejection fraction decline to less than 50% occurred. Conclusion Our data show encouraging efficacy of trastuzumab plus docetaxel therapy in patients with human epidermal growth factor receptor 2–positive SDC, with a manageable toxicity profile.

A clinicopathological study and prognostic factor analysis of 177 salivary duct carcinoma patients from The Netherlands

“…Although this is unusual, it is known from comparative studies that this may occur . Recently, preliminary data for 45 patients with HER2‐positive advanced unresectable SGC (of the ductal subtype) treated with docetaxel and trastuzumab in a phase 2 trial showed promising results, that is, overall response rate of 69%, median PFS of 11.3 months and median OS of 38.0 months . These results seem to support treating HER2‐positive SDC patients with trastuzumab plus docetaxel.…”

Prediction of clinical benefit from androgen deprivation therapy in salivary duct carcinoma patients

“…Besides ADT, other treatment options are available for patients with R/M SDC. In the case of ERBB2 (HER2) gene amplification (29.4–46.4%), patients can be treated with docetaxel plus trastuzumab, showing an overall response rate of 70.2% and median PFS of 8.9 months . Double HER2 blockade with docetaxel–trastuzumab–pertuzumab or in second‐line with the antibody‐drug conjugate trastuzumab‐emtansine also showed promising results .…”

“…In the case of ERBB2 (HER2) gene amplification (29.4-46.4%), 1,2 patients can be treated with docetaxel plus trastuzumab, showing an overall response rate of 70.2% and median PFS of 8.9 months. 8 Double HER2 blockade with docetaxel-trastuzumab-pertuzumab or in second-line with the antibody-drug conjugate trastuzumab-emtansine also showed promising results. [9][10][11] Finally, the high frequency (61.3%) of oncogenic driver gene mutations offers personalized treatment options.…”

Carboplatin and Docetaxel in Patients With Salivary Gland Carcinoma: A Retrospective Study

“…Furthermore, in some cases, beneficial effects were found when either carboplatin/docetaxel or CAB was administered and followed by the other after PD. In addition, we have also reported on the treatment with trastuzumab/ docetaxel in 57 patients with HER2-positive SDC and observed an ORR of 70% (7). All patients with SDC included in the current study were HER2negative; thus, the two studies cannot be compared due to the different molecular backgrounds.…”

“…We have previously reported an SDC classification system for the selection of an appropriate and personalized systemic therapy with anti-HER2, anti-AR, and/or cytotoxic drugs (26). We have also recently reported two prospective studies of anti-AR and anti-HER2 therapy that were based on this classification system (6,7). In a phase II study of CAB in 36 patients with AR-positive SGC, including 34 cases of SDC, an ORR of 42% was observed (6).…”