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Because the tyrosine kinases c-MET and vascular endothelial growth factor receptors (VEGFR) are often overexpressed in salivary gland cancer (SGC), this study evaluated the efficacy and safety of cabozantinib in patients with recurrent/metastatic (R/M) SGC. A single-centre phase II study was conducted. Patients with immunohistochemical c-MET-positive R/M SGC were included in three cohorts: adenoid cystic carcinoma (ACC); salivary duct carcinoma (SDC) and other miscellaneous SGCs. No prior systemic treatments were required. Patients started cabozantinib 60 mg once daily. The primary outcome was the objective response rate (ORR). Secondary outcomes included survival, safety and quality of life. Per Simon-two-stage design, depending on efficacy, a maximum of 43 patients would be included. In total, 25 patients were included until premature closure owing to severe toxicity. Six patients (24%) had grade 3–5 wound complications, occurring at a median of 7.1 months on cabozantinib treatment (range 2.1–12.6). Remarkably, four of these six patients developed this complication in the area prior exposed to high-dose radiotherapy. Other grade ≥3 adverse events in >1 patient were hypertension (20%), diarrhoea (8%) and dehydration (8%). Twenty-one patients were evaluable for response; 1/15 ACC (ORR: 7%); 1/4 SDC and 0/2 patients with other miscellaneous SGC responded. Median progression-free survival was 9.4 months (95% confidence interval [CI] 7.4–11.4 months), 7.2 months (95%CI 0.0–15.1) and 6.9 months (95%CI 0.0–15.1), respectively. This study showed too many severe cabozantinib-associated wound complications in patients with SGC, especially in prior irradiated areas. Therefore, the study closed prematurely. The efficacy in the limited number of evaluable patients was low to moderate. This trial was registered on ClinicalTrials.gov: NCT03729297. • Phase II study of cabozantinib in patients with salivary gland cancer. • Study closed prematurely owing to severe wound complications. • Wound complications occurred especially in prior irradiated areas. • The efficacy of cabozantinib was low to moderate in this study. • Caution with cabozantinib is advised in patients with prior high-dose radiotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Salivary duct carcinoma, an aggressive subtype of salivary gland cancer, is mostly androgen receptor‐positive. Only limited data are available on androgen deprivation therapy (ADT). Methods: Patients with advanced androgen receptor‐positive salivary duct carcinoma treated with first‐line ADT were retrospectively evaluated for clinical benefit (ie, partial response [PR] and stable disease, progression‐free survival [PFS] and overall survival [OS]). The OS was compared with patients with advanced salivary duct carcinoma who received best supportive care. Results: Thirty‐four of 35 patients who were ADT‐treated were evaluable: 6 patients had a PR (18%) and 11 had stable disease (32%) leading to a clinical benefit ratio of 50%. The median PFS for the ADT‐treated patients was 4 months and the median duration of clinical benefit was 11 months. The median OS was 17 months versus 5 months in 43 patients receiving best supportive care (P = .02). Conclusion: We recommend ADT in advanced androgen receptor‐positive salivary duct carcinoma given its response and clinical benefit. © 2017 Wiley Periodicals, Inc. Head Neck, 2017 [ABSTRACT FROM AUTHOR]

Objective: Three-dimensional organoid cell cultures have been established for a variety of human cancers. For most rare cancers, including salivary gland cancer (SGC), these models are lacking, despite the great unmet need to study cancer biology in these diseases. Therefore, we aimed to develop patient-derived organoid (PDO) models for different subtypes of SGC.Methods: Tumor samples of SGC patients were processed and embedded in Matrigel. Successful PDOs (expandable > 1*106 cells) were phenotypically characterized using immunohistochemistry (IHC) and genotypically by gene fusion analysis and by targeted and whole-exome sequencing. Successfully established PDOs were subjected to small-scale drug screening.Results: Out of 37 attempts, 7 viable short-term PDOs were established (19 % success rate; 3 salivary duct carcinoma, 3 adenoid cystic carcinoma and 1 mucoepidermoid carcinoma). Each PDO showed close phenotypical mimicry to parental tissue. Genotypic characterization revealed that in each PDO > 97.6 % of all COSMIC annotated variants and all MYB, MYBL1 and NFIB gene rearrangements were retained. Drug screening was proven feasible in all PDOs.Conclusion: We present the first comprehensively characterized short-term SGC PDO models for three subtypes of SGC with close phenotypic and genotypic resemblance to parental tissue, which can be used for drug screening applications. [ABSTRACT FROM AUTHOR]

Salivary gland cancer (SGC) is a rare malignancy consisting of 22 subtypes with different genetic, histological and clinical characteristics. This rarity and heterogeneity makes systemic treatment of recurrent or metastatic (R/M) disease challenging. Use of chemotherapy is scarcely studied and chemotherapy at best has moderate effects. New therapeutic strategies are therefore warranted, but advances made in SGC are lagging behind on advances made in more common cancers. By unraveling tumor characteristics of SGC, such as genetic alterations and protein expression profiles, therapeutic strategies tailored to the patient's tumor can be rationalized. This genomic profiling and mapping of immunohistochemical expression profiles is essential in the search for a suitable treatment approach. Thereby, it alleviates the paucity in systemic treatment options and can significantly alter the prognosis of patients with R/M SGC. This review aims to give a comprehensive overview of known genetic alterations and expression profiles amenable for targeted therapy in every histological subtype of SGC. We discuss the remaining knowledge gaps and the implications of these targets for future studies and personalized treatments, thereby aiding clinicians faced with this rare and heterogeneous type of cancer. [ABSTRACT FROM AUTHOR]

• Circulating tumour DNA can be detected in advanced SDC. • Longitudinal ctDNA analysis can be informative to understand disease dynamics in SDC. • ctDNA levels seem to correlate with radiological response in SDC. [ABSTRACT FROM AUTHOR]