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J Clin Med

Title:		FGFR Fusions as an Acquired Resistance Mechanism Following Treatment with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR TKIs) and a Suggested Novel Target in Advanced Non-Small Cell Lung Cancer (aNSCLC)
Author(s):		Raphael A; Dudnik E; Hershkovitz D; Jain S; Olsen S; Soussan-Gutman L; Ben-Shitrit T; Dvir A; Nechushtan H; Peled N; Onn A; Agbarya A; On Behalf Of The Israel Lung Cancer G;
Address:		"Department of Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv 6423906, Israel. Sackler Faculty of Medicine, Tel-Aviv University, P.O. Box 39040, Ramat Aviv, Tel-Aviv 6997801, Israel. Thoracic Oncology Service, Davidoff Cancer Center, Rabin Medical Center, Beilinson Campus, Petah Tikva 4941492, Israel. Department of Pathology, Tel-Aviv Sourasky Medical Center, Tel-Aviv 6423906, Israel. Guardant Health Asia Middle East and Africa, Singapore 138543, Singapore. Rhenium Oncotest Ltd., Ha-Satat St. 20, Modi'in-Maccabim-Re'ut 7177704, Israel. Department of Oncology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, P.O. Box 12000, Jerusalem 9112102, Israel. Department of Oncology, Shaare Zedek Medical Center, Jerusalem 9103102, Israel. Pulmonology Institute, Sheba Medical Center, Tel HaShomer, Ramat Gan 5262000, Israel. Department of Oncology, Bnai Zion Medical Center, Haifa 3339419, Israel"
Journal Title:		J Clin Med
Year:		2022
Volume:		20220428
Issue:		9
Page Number:		-
DOI:		10.3390/jcm11092475
ISSN/ISBN:		2077-0383 (Print) 2077-0383 (Electronic) 2077-0383 (Linking)
Abstract:		"BACKGROUND: FGFR1/2/3 fusions have been reported infrequently in aNSCLC, including as a rare, acquired resistance mechanism following treatment with EGFR TKIs. Data regarding their prevalence and therapeutic implications are limited. METHODS: The Guardant Health (GH) electronic database (ED) was evaluated for cases of aNSCLC and FGFR2/3 fusions; FGFR2/3 fusion prevalence with and without a co-existing EGFR mutation was assessed. The ED of Tel-Aviv Sourasky Medical Center (TASMC, June 2020-June 2021) was evaluated for cases of aNSCLC and de novo FGFR1/2/3 fusions. Patients with EGFR mutant aNSCLC progressing on EGFR TKIs and developing an FGFR1/2/3 fusion were selected from the ED of Davidoff Cancer Center (DCC) and Oncology Department, Bnei-Zion hospital (BZ) (April 2014-April 2021). Clinicopathological characteristics, systemic therapies, and outcomes were assessed. RESULTS: In the GH ED (n = 57,445), the prevalence of FGFR2 and FGFR3 fusions were 0.02% and 0.26%, respectively. FGFR3-TACC3 fusion predominated (91.5%). In 23.8% of cases, FGFR2/3 fusions co-existed with EGFR sensitizing mutations (exon 19 del, 64.1%; L858R, 33.3%, L861Q, 2.6%). Among samples with concurrent FGFR fusions and EGFR sensitizing mutations, 41.0% also included EGFR resistant mutations. In TASMC (n = 161), 1 case of de novo FGFR3-TACC3 fusion was detected (prevalence, 0.62%). Of three patients from DCC and BZ with FGFR3-TACC3 fusions following progression on EGFR TKIs, two received EGFR TKI plus erdafitinib, an FGFR TKI, with clinical benefit duration of 13.0 and 6.0 months, respectively. CONCLUSIONS: Over 23% of FGFR2/3 fusions in aNSCLC may be associated with acquired resistance following treatment with EGFR TKIs. In this clinical scenario, a combination of EGFR TKIs and FGFR TKIs represents a promising treatment strategy"
Keywords:		Fgfr FGFR fusion acquired resistance to EGFR TKIs ctDNA liquid biopsy lung cancer;
Notes:		"PubMed-not-MEDLINERaphael, Ari Dudnik, Elizabeth Hershkovitz, Dov Jain, Suyog Olsen, Steve Soussan-Gutman, Lior Ben-Shitrit, Taly Dvir, Addie Nechushtan, Hovav Peled, Nir Onn, Amir Agbarya, Abed On Behalf Of The Israel Lung Cancer Group eng Switzerland 2022/05/15 J Clin Med. 2022 Apr 28; 11(9):2475. doi: 10.3390/jcm11092475"