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)
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.
#1Katarzyna Błochowiak (Poznan University of Medical Sciences)H-Index: 8
#2Jerzy Sokalski (Poznan University of Medical Sciences)H-Index: 4
Last. Andrzej Marszałek (UMK: Nicolaus Copernicus University in Toruń)H-Index: 20
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Objectives Angiogenesis underlies tumour growth and metastasis through hepatocyte growth factor (HGF), epithelial growth factor (EGF), and vascular endothelial growth factor (VEGF). The aim of this study was to determine the levels of VEGF, EGF, HGF, HGFR (hepatocyte growth factor receptor), and SRSF1 (serine-rich protein splicing factor-1) in patients with parotid gland tumours and in healthy controls via ELISA in parotid saliva. Immunohistochemical expression of anti-angiogenic isoform of VEGF...
3 CitationsSource
#1Laura D. LocatiH-Index: 31
#2Donata GalbiatiH-Index: 5
Last. Lisa Licitra (University of Milan)H-Index: 67
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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...
5 CitationsSource
#1Katarzyna Błochowiak (Poznan University of Medical Sciences)H-Index: 8
#2Jerzy Sokalski (Poznan University of Medical Sciences)H-Index: 4
Last. Henryk Witmanowski (Poznan University of Medical Sciences)H-Index: 7
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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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Last. Michael F. BergerH-Index: 110
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MSK-IMPACT is a clinical sequencing platform able to detect genomic mutations, copy number alterations and structural variants in a panel of cancer-related genes. This assay is implemented prospectively to inform patient enrollment in genomically matched clinical trials at Memorial Sloan Kettering Cancer Center (MSKCC). Sequencing results of tumor and matched normal tissue from a cohort of >10,000 patients with detailed clinical annotation provide an overview of the genomic landscape of advanced...
1,278 CitationsSource
#1Salvatore Alfieri (University of Milan)H-Index: 14
#2Roberta Granata (University of Milan)H-Index: 16
Last. Laura D. Locati (University of Milan)H-Index: 31
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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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#1Renata Ferrarotto (University of Texas MD Anderson Cancer Center)H-Index: 23
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PurposeAdenoid cystic carcinomas (ACCs) represent a heterogeneous group of chemotherapy refractory tumors, with a subset demonstrating an aggressive phenotype. We investigated the molecular underpinnings of this phenotype and assessed the Notch1 pathway as a potential therapeutic target.MethodsWe genotyped 102 ACCs that had available pathologic and clinical data. Notch1 activation was assessed by immunohistochemistry for Notch1 intracellular domain. Luciferase reporter assays were used to confir...
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#1Laura D. LocatiH-Index: 31
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Last. Lisa LicitraH-Index: 67
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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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#1J.S. Ross (Albany Medical College)H-Index: 20
#3Kai Wang (ZJU: Zhejiang University)H-Index: 60
Last. Daniel W. Bowles (University of Colorado Denver)H-Index: 27
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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...
34 CitationsSource
#1Alan Loh HoH-Index: 10
#2Lara DunnH-Index: 14
Last. David G. PfisterH-Index: 81
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ABSTRACT Background Recurrent/metastatic adenoid cystic carcinoma (ACC) is an incurable disease with no standard treatments. The majority of ACCs express the oncogenic transcription factor MYB (also c-myb), often in the context of a MYB gene rearrangement. This phase II trial of the tyrosine kinase inhibitor (TKI) axitinib (Pfizer) tested the hypothesis that targeting pathways activated by MYB can be therapeutically effective for ACC. Patients and methods This is a minimax two-stage, phase II tr...
26 CitationsSource
Cited By4
#1Katherine C. Wai (UCSF: University of California, San Francisco)H-Index: 7
#2Hyunseok Kang (UCSF: University of California, San Francisco)H-Index: 24
Last. Patrick K. Ha (UCSF: University of California, San Francisco)H-Index: 41
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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.
#1Jessica L. Geiger (Cleveland Clinic)H-Index: 10
#2Nofisat Ismaila (American Society of Clinical Oncology)H-Index: 18
Last. Patrick K. Ha (UCSF: University of California, San Francisco)H-Index: 41
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PURPOSETo provide evidence-based recommendations for practicing physicians and other healthcare providers on the management of salivary gland malignancy.METHODSASCO convened an Expert Panel of medi...
#1Luigi Lorini (University of Brescia)H-Index: 2
#2Laura ArdighieriH-Index: 12
Last. Paolo Bossi (University of Brescia)H-Index: 39
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Abstract Adenoid cystic carcinoma (ACC) is a rare tumor, usually arising in the salivary gland, accounting for 1% of all head and neck cancers. ACC may have a long-term poor prognosis, as about 40% of radically treated patients will recur locoregionally and up to 60% will develop distant metastasis. Factors influencing risk of recurrence have been well studied, but few data exist about prognostic factors in Recurrent/Metastatic (RM) setting. Moreover, treatment of RM ACC is often a challenge for...
#1Despoina Pouloudi (UoA: National and Kapodistrian University of Athens)
#2Aristoteles Sotiriadis (UoA: National and Kapodistrian University of Athens)
Last. Stamatios Theocharis (UoA: National and Kapodistrian University of Athens)H-Index: 51
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Salivary gland carcinomas (SGCs) represent a group of rare tumors, with complete surgical resection being the main treatment option. Therapeutic armory for cases of locally aggressive, recurrent, and/or metastatic SGCs, though, remains poor since they exhibit high rates of resistance to systematic therapy. Angiogenesis is considered one of the contemporary hallmarks of cancer and anti-angiogenic factors have already been approved for the treatment of several cancer types. This review aims to sum...
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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