Patients with adenoid cystic carcinomas of the salivary glands treated with lenvatinib: Activity and quality of life

Published on May 1, 2020in Cancer5.742
· DOI :10.1002/CNCR.32754
Laura D. Locati31
Estimated H-index: 31
,
Donata Galbiati5
Estimated H-index: 5
+ 14 AuthorsLisa Licitra67
Estimated H-index: 67
(University of Milan)
Sources
Abstract
BACKGROUND: The treatment of patients with recurrent and/or metastatic (R/M) salivary gland adenoid cystic carcinoma (ACC) remains an unmet need. METHODS: Patients with R/M disease with a history of clinical or symptomatic disease progression within 6 months and a maximum of 1 previous line of chemotherapy or a multiple kinase inhibitor received oral lenvatinib at a dose of 24 mg/day. The primary endpoint was the objective response rate; secondary endpoints included quality of life (QOL) (according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Items [EORTC QLQ-C30] and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Module Head and Neck Module [EORTC QLQ-HN grade>/=3 in 50% of cases according to version 4.03 of the National Cancer Institute Common Terminology Criteria for Adverse Events). The dose of lenvatinib was reduced in 24 patients, whereas in 21 patients the dose was reduced within the first 12 weeks and 4 patients maintained the full dose throughout treatment. The QOL deteriorated between baseline and 6 months with regard to Fatigue and Dry Mouth. There was no evidence of changes in Swallowing and Physical Functioning. At a median follow-up of 29 months, 2 patients remained on treatment, 10 patients were off protocol for disease progression and were alive with disease, and 14 patients had died of disease progression. The median overall survival, progression-free survival, and duration of response were 27 months, 9.1 months, and 3.1 months, respectively. CONCLUSIONS: Lenvatinib appears to have modest activity in ACC. Toxicities are common but manageable and QOL was found to deteriorate in some domains.
References23
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#1Xiaofeng Liu (CSU: Central South University)H-Index: 1
#2Yunxiao Xu (CSU: Central South University)H-Index: 1
Last. Yan Yi (CSU: Central South University)H-Index: 1
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: Transcription factor MYB is essential for the tumorigenesis of multiple cancers, especially leukemia, breast cancer, colon cancer, adenoid cystic carcinoma and brain cancer. Thus, MYB has been regarded as an attractive target for tumor therapy. However, pioneer studies of antisense oligodeoxynucleotides against MYB, which were launched three decades ago in leukemia therapy, were discontinued because of their unsatisfactory clinical outcomes. In recent years, the roles of MYB in tumor transform...
14 CitationsSource
#1Patrick M. Dillon (UVA: University of Virginia)H-Index: 18
#2Gina R. Petroni (UVA: University of Virginia)H-Index: 41
Last. Christopher Y. Thomas (Wake Forest University)H-Index: 12
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Purpose: Genetic and preclinical studies have implicated FGFR signaling in the pathogenesis of adenoid cystic carcinoma (ACC). Dovitinib, a suppressor of FGFR activity, may be active in ACC. Experimental Design: In a two-stage phase II study, 35 patients with progressive ACC were treated with dovitinib 500 mg orally for 5 of 7 days continuously. The primary endpoints were objective response rate and change in tumor growth rate. Progression-free survival, overall survival, metabolic response, bio...
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#1Laura D. LocatiH-Index: 31
#2Federica PerroneH-Index: 41
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...
25 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...
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#1Alan Loh Ho (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 10
#2Eric J. Sherman (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 46
Last. David G. Pfister (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 81
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6096Background: Recurrent/metastatic adenoid cystic carcinoma (R/M ACC) is incurable. Regorafenib (BAY 73-4506; Bayer) is a tyrosine kinase inhibitor (TKI) that targets receptor tyrosine kinases (RTKs), including vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and platelet-derived growth factor receptor (PDGFR), each thought to be activated in ACC. In this phase II trial, we tested if regorafenib is an effective therapy for R/M ACC. Methods: Patient...
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#1Moran Amit (Technion – Israel Institute of Technology)H-Index: 29
#2Ayelet Eran (Technion – Israel Institute of Technology)H-Index: 4
Last. Ziv Gil (Technion – Israel Institute of Technology)H-Index: 12
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Head and neck malignancies have the propensity to invade nerves. Perineural tumor invasion is common, with some series reporting rates of 30 to 100%. Squamous cell carcinoma and adenoid cystic carcinoma are the most commonly involved tumors. The most commonly involved nerves are the trigeminal (cranial nerve [CN] V) and facial (CN VII) and their branches. Neural spread away from a tumor is encountered less often and usually causes specific symptoms such as pain, muscle weakness, and atrophy, dep...
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#1Stuart J. Wong (MCW: Medical College of Wisconsin)H-Index: 26
#2Theodore Karrison (U of C: University of Chicago)H-Index: 88
Last. Ezra E.W. Cohen (UCSD: University of California, San Diego)H-Index: 78
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Abstract Adenoid cystic carcinoma (ACC) is a subtype of malignant salivary gland tumors (MSGT), in which 90% of cases express cKIT. Dasatinib is a potent and selective inhibitor of five oncogenic protein tyrosine kinases (PTKs)/kinase families including cKIT. We conducted a phase II study to determine the antitumor activity of dasatinib in ACC and non-ACC MSGT. In a two-stage design, patients with progressive, recurrent/metastatic ACC (+cKIT) and non-ACC MSGT (separate cohort) were treated with ...
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#1Bhumsuk Keam (SNU: Seoul National University)H-Index: 47
#2Sung-Bae Kim (UOU: University of Ulsan)H-Index: 57
Last. Yung-Jue Bang (SNU: Seoul National University)H-Index: 107
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BACKGROUND The objective of this study was to evaluate the efficacy and safety of dovitinib in patients with adenoid cystic carcinoma (ACC). METHODS ACC patients with documented disease progression within the past 12 months were eligible. Patients received oral dovitinib (500 mg once daily for 5 consecutive days followed by a 2-day rest every week) until disease progression or unacceptable toxicities. The primary endpoint was the probability of 4-month progression-free survival (PFS). Metabolic ...
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#1John A. Jakob (University of Texas MD Anderson Cancer Center)H-Index: 9
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Background The purpose of this study was to determine the antitumor activity of the epidermal growth factor receptor (EGFR) inhibitor gefitinib in patients with recurrent/metastatic salivary gland cancer. Methods We conducted a phase II study in adenoid cystic carcinoma (ACC) and non-ACC. Gefitinib was administered 250 mg orally daily. The primary endpoint was tumor response. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and disease control rates. EGFR and ...
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#1Martin Schlumberger (Université Paris-Saclay)H-Index: 115
#2Makoto TaharaH-Index: 47
Last. Steven I. ShermanH-Index: 86
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Background Lenvatinib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, platelet-derived growth factor receptor α, RET, and KIT, showed clinical activity in a phase 2 study involving patients with differentiated thyroid cancer that was refractory to radioiodine (iodine-131). Methods In our phase 3, randomized, double-blind, multicenter study involving patients with progressive thyroid cancer that was refractory to iodi...
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#1James Nightingale (UQ: University of Queensland)
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Abstract The natural history of adenoid cystic carcinoma (ACC) is relentless, defined by treatment failure heralded by reasonable locoregional recurrence and poor long-term distant metastatic disease. In this review, we present an update of clinical features, molecular classification, current targeted therapies, immune landscapes and novel treatment targets with their respective clinical trials. The presented results are defined by a lack of overall response rate and limited progression free sur...
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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...
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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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