Phase II Study of Lapatinib in Recurrent or Metastatic Epidermal Growth Factor Receptor and/or erbB2 Expressing Adenoid Cystic Carcinoma and Non–Adenoid Cystic Carcinoma Malignant Tumors of the Salivary Glands

Agulnik, Mark; Cohen, Ezra; Cohen, Roger B.; Chen, Eric X.; Vokes, Everett E.; Hotte, Sébastien J.; Winquist, Eric; Laurie, Scott A.; Hayes, D. Neil; Dancey, Janet; Brown, Shirley; Pond, Gregory R.; Lorimer, Ian A. J.; Daneshmand, Manijeh; Ho, J. C.; Tsao, Ming‐Sound; Siu, Lillian L.

doi:10.1200/jco.2007.11.8612

Cited by 241 publications

(173 citation statements)

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“…42 A recent phase II study of lapatinib, a dual inhibitor of EGFR and HER2 activity, in recurrent or metastatic EGFR and/or HER2-expressing adenoid cystic carcinomas and other malignant tumors of the salivary glands has been conducted to evaluate its antitumoral activity. 43 This study found that lapatinib probably has a cytostatic effect on carcinomas of salivary glands, but no objective clinical responses were detected. The relationship of EGFR expression, mutational status and copy number to therapy response has not been yet evaluated in these tumors.…”

Section: Discussionmentioning

confidence: 69%

Salivary gland-type lung carcinomas: an EGFR immunohistochemical, molecular genetic, and mutational analysis study

Macarenco¹,

Uphoff

Gilmer

et al. 2008

Modern Pathology

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Salivary gland-type lung carcinomas are uncommon neoplasms of the lung, the two most common being adenoid cystic carcinoma and mucoepidermoid carcinoma. Although they usually have an indolent behavior, adenoid cystic carcinomas can be more aggressive, with 5-year survival as low as 55%. Unfortunately, these tumors do not respond well to chemotherapy. In contrast to the most common subtypes of lung carcinomas, epidermal growth factor receptor studies have not been carried out in this group of tumors. Herein we report a series of 24 cases (12 adenoid cystic and 12 mucoepidermoid carcinomas) tested for epidermal growth factor receptor protein expression, epidermal growth factor receptor gene copy gains, and epidermal growth factor receptor gene mutational status, through immunohistochemistry, fluorescence in situ hybridization, and sequencing of the exons 18-21, respectively. Overall, 91 and 92% of the adenoid cystic carcinomas and mucoepidermoid carcinomas expressed epidermal growth factor receptor protein. Chromosome 7 polysomy occurred in 25% of the cases (four adenoid cystic carcinomas and two mucoepidermoid carcinomas). No epidermal growth factor receptor gene amplification was detected and no mutation was found in exons 18-21 of the epidermal growth factor receptor gene. Immunoexpression of epidermal growth factor receptor in salivary gland-type lung carcinomas is not related to epidermal growth factor receptor gene copy number or mutational status. Keywords: salivary gland-type lung carcinoma; adenoid cystic carcinoma; mucoepidermoid carcinoma; epidermal growth factor receptor; immunohistochemistry; FISH Salivary gland-type lung carcinomas are uncommon, representing less than 1% of all lung tumors. Adenoid cystic carcinoma and mucoepidermoid carcinoma are the two most common subtypes. 1,2 Salivary gland-type lung carcinomas are generally reported as having a good prognosis. Indeed, mucoepidermoid carcinoma usually presents as a localized disease that can be completely resected with surgery and the reported 5-and 10-year survivals rates are both 87%. 3 However, patients with mucoepidermoid carcinomas can develop local or distant metastasis, which are typically unresponsive to conventional chemotherapy and radiation. In contrast, adenoid cystic carcinoma tends to present at a higher stage, is often unresectable, or, if resected, often has positive margins and subsequent local recurrences. The prognosis is also poorer with recent reported 5-and 10-year survivals of 55 and 39%, respectively. 3 As with mucoepidermoid carcinoma, the survival does not appear to be affected by traditional chemotherapy and radiation. Therefore, there appears to be a potential use for targeted novel therapies in the care of these patients.

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Section: Discussionmentioning

confidence: 69%

Salivary gland-type lung carcinomas: an EGFR immunohistochemical, molecular genetic, and mutational analysis study

Macarenco¹,

Uphoff

Gilmer

et al. 2008

Modern Pathology

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“…The median progression‐free survival (PFS) was 64 months and the overall survival rate was 100% for localized disease, whereas median PFS was 13 months and the overall survival was 24 months 72. Agulnik et al73 conducted a phase II trial for patients whose tumors expressed EGFR and/or HER‐2. Those patients were given lapatinib, an agent that blocks signaling by both receptors.…”

Section: Introductionmentioning

confidence: 99%

Adenoid cystic carcinoma: A review of recent advances, molecular targets, and clinical trials

Chakraborty²,

et al. 2015

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BackgroundAdenoid cystic carcinoma (ACC) is a rare tumor of secretory glands. In this study, recent advances in molecular characterization and in therapeutics are reviewed.MethodsA search of articles in PubMed and of abstracts from national meetings was performed regarding ACC.ResultsRecent genetic analyses found that recurrent chromosome 6:9 translocations in ACC generate an MYB:NFIB gene fusion resulting in overexpression of the MYB oncoprotein. Several other frequent mutations are recently published that may be relevant for drug development. Several trials of targeted drugs are reviewed. Some agents delay tumor progression, but tumor responses remain rare.ConclusionACCs have a characteristic chromosomal translocation, but also frequently pick up additional mutations. Clinical research is limited by the rarity and slow growth of ACC. Several ongoing trials are testing agents that inhibit fibroblast growth factor receptor signaling or other signaling pathways. Novel treatments based on the recently sequenced tumor genome are under development. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc. 38: 620–627, 2016

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“…Epidermal growth factor (EGFR; also known as ErbB1) is considered a possible key pathway for therapeutic molecules. Overexpression of EGFR has been shown in both salivary ACC and non-ACC (Agulnik et al, 2007;Ettl et al, 2008), and these findings have provided the motivation for trials with EGFR inhibitor-based therapies. Anti-EGFR agents include (1) monoclonal antibodies (cetuximab or erbitux, panitumumab), which block the binding of natural EGFR ligands, such as EGF or TGF-a, resulting in inhibition of downstream signal transduction pathways and (2) small molecule tyrosine kinase inhibitors (TKIs), which act by binding the ATP pocket within the kinase domain of the EGFR and impairing its catalytic activity (gefitinib, erlotinib and lapatinib).…”

mentioning

confidence: 99%

“…Gefitinib was associated with a 53% stable disease rate (10/19) in ACC, but had no effects in patients with salivary duct tumours and mucoepidermoid cancer (Glisson et al, 2005). Lapatinib, inhibiting ErbB1 and ErbB2 tyrosine kinases, was studied in a phase II trial and stabilized disease for greater than 6 months in 47% of ACC patients (Agulnik et al, 2007).…”

mentioning

confidence: 99%

Epidermal growth factor receptor kinase domain mutations are rare in salivary gland carcinomas

et al. 2009

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Activating mutations within the epidermal growth factor (EGFR) tyrosine kinase domain identify non-small cell lung cancer patients with improved clinical response to tyrosine kinase inhibitor therapy. Recently, we identified two EGFR mutations in a cohort of 25 salivary gland carcinomas (SGCs) by screening the tumour samples for the both most common hotspot mutations in exons 19 and 21 by allele-specific PCR. Here, we present a comprehensive sequencing analysis of the entire critical EGFR tyrosine kinase domain in 65 SGC of the main histopathological types. We found EGFR mutations in the tyrosine kinase domain to be a rare event in SGCs. No additional mutations other than the two known exon 19 deletions (c.2235_2249del15) in a mucoepidermoid carcinoma and an adenoid cystic carcinoma have been detected. Other putative predictive markers for EGFR-targeted therapy in SGCs might be relevant and should be investigated.

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Phase II Study of Lapatinib in Recurrent or Metastatic Epidermal Growth Factor Receptor and/or erbB2 Expressing Adenoid Cystic Carcinoma and Non–Adenoid Cystic Carcinoma Malignant Tumors of the Salivary Glands

Cited by 241 publications

References 39 publications

Salivary gland-type lung carcinomas: an EGFR immunohistochemical, molecular genetic, and mutational analysis study

Salivary gland-type lung carcinomas: an EGFR immunohistochemical, molecular genetic, and mutational analysis study

Adenoid cystic carcinoma: A review of recent advances, molecular targets, and clinical trials

Epidermal growth factor receptor kinase domain mutations are rare in salivary gland carcinomas

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