Phase II trial with axitinib in recurrent and/or metastatic salivary gland cancers of the upper aerodigestive tract.

Published on Oct 1, 2019in Head and Neck-journal for The Sciences and Specialties of The Head and Neck2.538
· DOI :10.1002/HED.25891
Laura D. Locati31
Estimated H-index: 31
,
Stefano Cavalieri8
Estimated H-index: 8
+ 13 AuthorsLisa Licitra67
Estimated H-index: 67
(University of Milan)
Sources
Abstract
BACKGROUND: Patients with prognosis recurrent/metastatic (R/M) salivary gland carcinomas (SGCs) are poor. Activity of axitinib was demonstrated in adenoid cystic carcinoma (ACC). We tested axitinib in a larger cohort of R/M SGCs including non-ACC. METHODS: Axitinib was administered at 10 mg daily (dose escalation allowed) until progression or unacceptable toxicity. Null hypothesis would be rejected if more than 3 of 26 responses were observed. RESULTS: Twenty-six patients (50% were male; 6 ACC, 20 non-ACC) were treated. Response rate was 8% (2 partial responses), 13 stable disease (>6 months in 7 patients) and 11 disease progression. Median progression-free survival and overall survival were 5.5 and 26.2 months, respectively. All patients had at least one adverse event: stomatitis (69%), fatigue (58%) and hypertension (54%) were the most frequent. CONCLUSIONS: This trial did not meet its primary endpoint hence axitinib should not be considered for further investigations in SGCs. Safety profile was in line with the scientific literature.
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#2Jerzy Sokalski (Poznan University of Medical Sciences)H-Index: 4
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#1Laura D. LocatiH-Index: 31
#2Donata GalbiatiH-Index: 5
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6086Background: Systemic chemotherapy and targeted therapies (TT) are almost ineffective in R/M ACC patients (pts). Sorafenib and axitinib showed some activity, possibly through their antiangiogeni...
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#1Katarzyna Błochowiak (Poznan University of Medical Sciences)H-Index: 8
#2Jerzy Sokalski (Poznan University of Medical Sciences)H-Index: 4
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BACKGROUND: Vascular endothelial growth factor (VEGF) is an angiogenic factor and could be involved in the pathogenesis of salivary gland tumors. VEGF exerts its biological function by binding to its receptors, VEGFR1 and VEGFR2. An alternative splice variant of VEGF (VEGFxxxb) is an anti-angiogenic factor. Binding VEGF165b with VEGFR2 results in an impaired angiogenic response. The imbalance of VEGFxxx and VEGFxxxb isoforms can underpin pathological angiogenesis. OBJECTIVES: The purpose of this...
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Abstract Salivary gland carcinomas (SGCs) represent one of the most complex tumors from a pathological point of view. According to the World Health Organization (WHO) classification (2005), twenty-four malignant histotypes are recognized, almost all characterized by specific morphological and genetic features as well as by particular clinical behavior. Loco-regional relapse and distant metastases are quite common. Distant metastases are diagnosed in 25–55% of the patients and only 20% of them ar...
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Abstract Background Pre-clinical and clinical evidence suggests a rationale for the use of anti-angiogenic agents, including sorafenib, in recurrent and/or metastatic salivary gland carcinomas (RMSGCs). This study evaluates the activity of sorafenib in patients with RMSGCs and also investigates whether the activity of sorafenib could be related to its main tailored targets (i.e. BRAF, vascular endothelial growth factor receptor 2 [VEGFR2], platelet-derived growth factor receptor α [PDGFRα] and β...
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ABSTRACT Background Relapsed/metastatic salivary gland carcinomas (SGCs) have a wide diversity of histologic subtypes associated with variable clinical aggressiveness and response to local and systemic therapies. We queried whether comprehensive genomic profiling could define the tumor subtypes and uncover clinically relevant genomic alterations, revealing new routes to targeted therapies for patients with relapsed and metastatic disease. Patients and methods From a series of 85 686 clinical cas...
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Despite aggressive initial interventions, recurrent/metastatic salivary gland cancer is not uncommon. Standard chemotherapy has not been shown to have durable clinical benefits. Several potential molecular markers have been identified in different histologic subtypes of salivary cancers. The objective of this review is to highlight the molecular markers that have been targeted in clinical trials for salivary gland cancers.
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Salivary gland carcinomas (SGCs) account for <5% of head and neck malignant neoplasms, further subcategorized in over 20 histological subtypes. For the most part, treatment for advanced disease is guided by morphology. SGCs in general respond poorly to a wide array of standard chemotherapy, with short durability, and significant toxicity. More recently, next-generation sequencing provided significant input on the molecular characterization of each SGC subtype, not only improving diagnostic diffe...
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