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.

BackgroundThere is no standard first-line chemotherapy for recurrent/metastatic (RM) or unresectable locally advanced (LA) salivary gland carcinoma (SGC).Patients and methodsWe conducted a single institution, open-label, single arm, phase II trial of combined androgen blockade (CAB) for androgen receptor (AR)-positive SGC. Leuprorelin acetate was administered subcutaneously at a dose of 3.75 mg every 4 weeks. Bicalutamide was administered orally at a daily dose of 80 mg. Patients were treated until progressive disease or unacceptable toxicities.ResultsThirty-six eligible patients were enrolled. Thirty-three patients had RM disease and three patients had LA disease. The pathological diagnoses were salivary duct carcinoma (34 patients, 94%) and adenocarcinoma, NOS (two patients, 6%). The best overall response rate was 41.7% [n = 15, 95% confidence interval (CI), 25.5%–59.2%], the clinical benefit rate was 75.0% (n = 27, 95% CI, 57.8%–87.9%). The median progression-free survival was 8.8 months (95% CI, 6.3–12.3 months) and the median overall survival was 30.5 months (95% CI, 16.8 months to not reached). Additional analyses between treatment outcomes and clinicopathological factors or biomarkers including AR positivity, human epidermal growth factor receptor 2 status, and its complex downstream signaling pathway gene mutations showed no statistically significant differences. Elevated grade 3 liver transaminases and increased serum creatinine were reported in two patients, respectively. Discontinuation of leuprorelin acetate or bicalutamide due to adverse event occurred in one patient.ConclusionThis study suggests that CAB has equivalent efficacy and less toxicity for patients with AR-positive RM or unresectable LA SGC compared with conventional chemotherapy, which warrants further study.Clinical Trial RegistrationUMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703

The statuses of some molecules are useful to predict DFS in patients with SDC. Ki-67 overexpression suggests that cytotoxic agents are effective for SDC. Since the majority of SDCs express AR, HER2, and/or EGFR, assessing and targeting these molecules are promising strategies to improve the prognosis of unresectable, metastatic or recurrent SDC, and a classification system according to the molecular expression status may be useful to select appropriate therapy.

Although immune-checkpoint inhibitors (ICIs) are effective against various cancers, little is known regarding their role in salivary gland carcinoma (SGC) treatment. Therefore, we evaluated the efficacy and safety of nivolumab monotherapy in patients with recurrent and/or metastatic SGC. In this multicentre retrospective study, nivolumab (240 mg) was administered every 2 weeks. The overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety were examined; the correlation between treatment outcomes and clinicopathological factors was analysed. Twenty-four patients were enrolled; the most common histopathology was salivary duct carcinoma. Eleven tumours were PD-L1-positive; no tumour was microsatellite instability-high. The ORR was 4.2%, and the median PFS and OS were 1.6 and 10.7 months, respectively. One patient continued nivolumab for 28 months without disease progression. One patient showed grade 4 increase in creatine phosphokinase levels and grade 3 myositis. Biomarker analysis revealed significantly increased OS in patients with performance status of 0; modified Glasgow prognostic score of 0; low neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and C-reactive protein; and high lymphocyte-to-monocyte ratio and in patients who received systemic therapy following nivolumab. Although nivolumab’s efficacy against SGC was limited, some patients achieved long-term disease control. Further studies are warranted on ICI use for SGC.

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Background/Aim: The treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has remained challenging. The effect of salvage chemotherapy (SCT) after nivolumab has been identified recently in other cancer types. The aim of this study was to examine the efficacy of SCT after nivolumab treatment in patients with R/M HNSCC. Patients and Methods: A retrospective study was conducted at four institutions in Japan. Fifty-six patients were enrolled in the study. Results: The overall survival (OS) in SCT patients was significantly longer than that in best supportive care (BSC) patients. In the SCT patients, the median OS, median progression-free survival (PFS) and objective response rate (ORR) were 7.3 months, 2.3 months and 36%, respectively. Prognostic factor for OS and ORR was performance score (PS) and previous radiation, respectively. Conclusion: SCT after nivolumab is associated with better clinical outcomes in patients with R/M HNSCC compared to those receiving BSC.Head and neck cancer accounts for 8% of all cancer cases worldwide; approximately 1,450,000 new cases are diagnosed, along with 500,000 cancer-related deaths registered annually (1). The prognosis of patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is generally poor, with a median overall survival (mOS) of <1 year. Moreover, identifying the optimal treatment for R/M HNSCC has remained challenging. The EXTREME study in 2008 showed a mOS of 10.1 months, median progression-free survival (mPFS) of 5.6 months and objective response rate (ORR) of 36% in the first-line setting (2). This regimen was combined with cetuximab, 5-fluorouracil and cisplatin/carboplatin (3). Further, the CheckMate-141 study in 2016 with nivolumab indicated a mOS of 7.5 months, mPFS of 2.0 months, and ORR of 13.3% in the second-line setting (4). Additionally, nivolumab was associated with better clinical outcome in recurrent HNSCC patients in the real-world setting (5, 6). However, phase III trials for the third-line setting have not been described in patients with R/M HNSCC. In the recent KEYNOTE-048 study, pembrolizumab treatment with or without chemotherapy in patients with positive programmed death-ligand 1 (PD-L1) expression showed significantly improved overall survival (OS) compared to that observed in the EXTREME regimen (7). Hence, it is necessary to consider treatment measures after immune checkpoint inhibitors (ICIs).Few recent studies have reported that salvage chemotherapy (SCT) after ICIs might be useful in patients with non-small-cell lung cancer (NSCLC). In the two CheckMate studies comparing nivolumab with docetaxel in the second-line setting, nivolumab was found to confer longer OS than docetaxel (8, 9). In the OAK study, patients 5277

Background Tumors in the parapharyngeal space are rare, and preoperative diagnosis is difficult because of anatomical and histological complexity. Methods To evaluate the usefulness of preoperative diagnosis, we compared the classification of tumor localization in the prestyloid and retrostyloid compartments by imaging and preoperative cytological diagnosis by fine‐needle aspiration cytology with the postoperative histopathological diagnosis in 120 patients with tumors in the parapharyngeal space. Results Tumors were located in the prestyloid and retrostyloid compartments in 68 and 52 patients, respectively. The majority of histopathological diagnoses in the prestyloid and retrostyloid compartments were pleomorphic adenoma and schwannoma, respectively. All malignant tumors were in the prestyloid compartment. The preoperative cytological diagnostic rate for benign or malignant tumor was 95.2%, which was not inferior to that for other head and neck lesions. Conclusion Our results suggested that the preoperative classification of tumor localization and cytological diagnosis improved the accuracy of presumptive diagnosis.

Background/Aim: Head and neck cancers account for 8% of all cancer cases worldwide. However, identifying the optimal treatment for recurrent or metastatic head and neck cancer (R/MHNSCC) has been challenging. The aim of this study was to evaluate the efficacy, safety, and prognostic factors of the outcome of patients with R/MHNSCC who were treated with weekly cetuximab and paclitaxel (Cmab-PTX). Patients and Methods: The records of R/MHNSCC patients who were treated with Cmab-PTX in our institution between June 2013 and September 2017 were collected. We analyzed Overall survival (OS), progression-free survival (PFS), prognostic factors and adverse events. Results: The records of 59 patients treated with Cmab-PTX were analyzed. The median PFS was 5.7 months, and the median OS was 11.8 months. Patients who had been administered cetuximab previously had shorter PFS and OS than those who had not. Conclusion: Cmab-PTX may be considered as a treatment option in head and neck R/MHNSCC patients.