Possible differential EGFR-TKI efficacy among exon 19 deletional locations in EGFR-mutant non-small cell lung cancer

Kaneda, Toshihiko; Hata, Akito; Tomioka, Haruaki; Tanaka, Kosuke; Kaji, Ryuji; Fujita, Shiro; Tomii, Keisuke; Katakami, Nobuyuki

doi:10.1016/j.lungcan.2014.09.014

Cited by 27 publications

(45 citation statements)

References 15 publications

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“…According to the Somatic Mutations in EGFR Database, the most frequent Del-19 in lung adenocarcinomas is delE746-A750 (28.89%), followed by delL747-P753insS (2.49%) and delL747-A750insP (1.73%). 10 However, the EGFR deletion in three of our CMPTs was delE746-T751/S752V, and this deletion is extremely rare in lung adenocarcinomas (only one reported case). 10 In addition, that particular case likely did not involve a CMPT, because cilia were not documented.…”

Section: Discussionmentioning

confidence: 64%

Frequent BRAF or EGFR Mutations in Ciliated Muconodular Papillary Tumors of the Lung

Kamata

Sunami

Yoshida

et al. 2016

Journal of Thoracic Oncology

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Section: Discussionmentioning

confidence: 64%

Frequent BRAF or EGFR Mutations in Ciliated Muconodular Papillary Tumors of the Lung

Kamata

Sunami

Yoshida

et al. 2016

Journal of Thoracic Oncology

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“…The latter two mutation types have not yet been reported in CMPTs. An initial study suggested that CMPTs are not a precursor for common lung cancer because the mutation types detected in CMPTs − BRAF (V600E) and EGFR (del E746‐T751/S752V) − are rare in common lung cancers . However, KRAS oncogene mutations (G12X), which are common in mucinous adenocarcinomas, have been identified (COSMIC: http://cancer.sanger.ac.uk/cosmic/).…”

Section: Discussionmentioning

confidence: 99%

A molecular pathological study of four cases of ciliated muconodular papillary tumors of the lung

Kataoka

Okihara

Matsumura

et al. 2018

Pathology International

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Ciliated muconodular papillary tumors (CMPTs) are a recently categorized benign or low-grade malignant neoplasm that develops in the peripheral lung. Only about 40 cases have been reported to date, and the clinicopathological characteristics have yet to be defined in detail. Here, we present four cases of CMPTs with a focus on their immunohistochemical profiles and driver gene mutations. These tumors were a papillary proliferation of a mixture of ciliated, mucous, and basal cells located in the peripheral lung. Ciliated, mucous and basal cells were positive for TTF-1 when using the clone SPT24, but negative for HNF-4α. Basal cells were positive for p40. Mucous cells in some tumors were positive for MUC5AC and MUC6. The Ki-67 index was less than 5%, and strong expression of p53 was not detected. Three of the four tumors had a BRAF (V600E) driver mutation, an EGFR (del E746-T751/S752V) driver mutation, or driver mutations in both EGFR (E709G) and KRAS (G12V). These mutation types are rare for any histological type of lung cancer. The present results confirmed that CMPT is a neoplasm with immunohistochemical features and driver gene mutations that are distinct from those of common lung tumors.

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“…The clinical data are controversial: the largest study by Chung et al . reported that ORR to 1G‐TKI in Del starting at E746 were lower than those in Del starting at L747 (68.2% and 79.6%, respectively), whereas other groups showed the opposite tendency . Notably, ORR in 7 patients with Del starting at 748, 751 or 752 was only 43% …”

Section: Treatment Strategy By Mutation‐specific Tyrosine Kinase Inhimentioning

confidence: 99%

“…Del19 includes at least 30 variants . Deletion starting at E746 (the majority of them are delE746_A750), E747 and others are present in 73% (272/373), 25% (92/373) and 2% (9/373), respectively . Rare variant delE746_S752insV may be less sensitive to gefitinib according to the in vitro data (Table ) .…”

Section: Treatment Strategy By Mutation‐specific Tyrosine Kinase Inhimentioning

confidence: 99%

“…(53) Deletion starting at E746 (the majority of them are delE746_A750), E747 and others are present in 73% (272/373), 25% (92/373) and 2% (9/ 373), respectively. (53)(54)(55) Rare variant delE746_S752insV may be less sensitive to gefitinib according to the in vitro data ( Table 2). (56)(57)(58) The clinical data are controversial: the largest study by Chung et al reported that ORR to 1G-TKI in Del starting at E746 were lower than those in Del starting at L747 (68.2% and 79.6%, respectively), (53) whereas other groups showed the opposite tendency.…”

Section: Treatment Strategy By Mutation-specific Tyrosine Kinase Inhimentioning

confidence: 99%

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Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy

2016

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Somatic mutations in the epidermal growth factor receptor (EGFR) gene are present in approximately 20% (in Caucasians) to 40% (in East Asians) of adenocarcinomas of the lung. Targeted therapy for these lung cancers has been established based on evidence regarding mainly common mutations; that is, exon 19 deletions (Del19) and L858R. EGFR‐tyrosine kinase inhibitors (TKI), gefitinib, erlotinib or afatinib showed high objective response rates (ORR) of approximately 60%. Several studies suggested that Del19 might be more sensitive to EGFR‐TKI than L858R. On the other hand, it has been difficult to establish evidence for other less common mutations, accounting for 12% of all EGFR mutations, because there are many variants and many studies have excluded patients with these uncommon mutations. However, recent studies revealed that these rare genotypes could be targetable if appropriate TKI are selected. For example, G719X (X denotes A, S, C and so on), Del18, E709K, insertions in exon 19 (Ins19), S768I or L861Q showed moderate sensitivities to gefitinib or erlotinb with ORR of 30%–50%. However, afatinib appeared to be especially effective for these tumors. Although Ins20s (except for insFQEA) have been regarded as resistant mutations, osimertinib may be effective for rare subtypes of them and nazartinib (EGF816) is promising for the majority of them. For the further development of targeted therapy in all EGFR mutations, it is important to precisely detect targetable mutations, to select the most appropriate TKI for each mutation, and to continue investigating in vitro studies and collecting clinical data on even rare mutations.

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Possible differential EGFR-TKI efficacy among exon 19 deletional locations in EGFR-mutant non-small cell lung cancer

Cited by 27 publications

References 15 publications

Frequent BRAF or EGFR Mutations in Ciliated Muconodular Papillary Tumors of the Lung

Frequent BRAF or EGFR Mutations in Ciliated Muconodular Papillary Tumors of the Lung

A molecular pathological study of four cases of ciliated muconodular papillary tumors of the lung

Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy

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