Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23


15P - FGFR3-TACC3 fusion (F) as an acquired resistance mechanism following treatment with EGFR TKIs and a suggested novel target in aNSCLC


06 Oct 2021




Raphael Ari


Annals of Oncology (2021) 32 (suppl_6): S1345-S1371. 10.1016/annonc/annonc740


R. Ari1, E. Dudnik2, D. Hershkovitz3, S.S. Jain4, L. Soussan-Gutman5, T. Ben Shitrit5, H. Nechushtan6, N. Peled7, A. Agbarya8

Author affiliations

  • 1 Tel Aviv Sourasky Medical Center (Ichilov), Tel Aviv/IL
  • 2 Rabin Medical Center Davidoff Cancer Centre, Beilinson Campus, 4941492 - Petah Tikva/IL
  • 3 Tel Aviv Sourasky Medical Center (Ichilov), 64239 - Tel Aviv/IL
  • 4 Guardant Health Pte. Ltd., 138543 - Singapore/SG
  • 5 rhenium, Tel-Aviv/IL
  • 6 Hadassah University Hospital - Ein Kerem, 91120 - Jerusalem/IL
  • 7 Shaare Zedek Medical Center, 9103102 - Jerusalem/IL
  • 8 Bnai Zion Medical Center, 31048 - Haifa/IL

Abstract 15P


Fusion between FGFR3 and TACC3 represents a rare acquired resistance mechanism following treatment with EGFR TKIs. Data regarding its prevalence and therapeutic implication is limited.


Guardant Health (GH) clinical electronic database (ED) (11/2016-07/2021) was evaluated for cases of aNSCLC and FGFR2/3 F; prevalence FGFR2/3 F with and without a co-existing EGFR M was assessed (we hypothesized that cases with co-existing FGFR2/3 F and EGFR M reflect the cases of FGFR-driven resistance following EGFR TKIs). ED of Tel-Aviv Sourasky Medical Center (TASMC, a referral center for upfront molecular testing; 161 aNSCLC patients (pts) included in 06/2020-06/2021) was evaluated for cases of aNSCLC and de novo FGFR1/2/3 F; prevalence of de novo FGFR1/2/3 F with or without EGFR M was assessed. Pts with EGFR M aNSCLC progressing on EGFR TKIs that developed an FGFR3-TACC3 F were selected from the ED of Davidoff Cancer Center (DCC) and Oncology Department, Bnei-Zion hospital (BZ) (04/2014-04/2021, n=3). Clinico-pathological pt characteristics, systemic therapies and outcomes were assessed.


In GH database, the prevalence of FGFR2 F and FGFR3 F were 0.02% and 0.24%, respectively. Of FGFR3 F, 99.3% were FGFR3-TACC3 F. Of FGFR3-TACC3 F, EGFR M co-existed in 22.6% (exon 19 del, 64%; L858R, 33%, L861Q, 3%). In TASMC, 1 case of de novo FGFR3-TACC3 F (without EGFR M) was detected (prevalence, 0.62%). Characteristics of the 3 selected pts from DCC and BZ ED are provided in the table. Combination of EGFR TKI + FGFR TKI was initiated in 2 pts: 1st pt achieved a partial response with gefitinib + erdafitinib for 7+ months at the time of the report; 2nd pt recently initiated osimertinib+erdafitinib. No safety signals were seen. Table: 15P

Pt Sex Age Previous therapy EGFR M type FGFR3-TACC3 detection method FGFR3-TACC3 FMAF, %
1 F 64 Gefitinib, osimertinib L858R Guardant 360 0.3
2 F 64 Gefitinib, osimertinib L747_A750delinsP Guardant 360 0.07
3 M 85 Osimertinib E746_A750del Guardant 360 0.04


Up to 23% of FGFR3-TACC3 F in aNSCLC are associated with acquired resistance following treatment with EGFR TKIs. In this clinical scenario, combination of EGFR TKI and FGFR TKI represents a promising treatment strategy.

Legal entity responsible for the study

Israel Lung Cancer Group; Guardant Health.


Has not received any funding.


E. Dudnik: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: BI; Financial Interests, Personal, Research Grant: AZ; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: MSD. S.S. Jain: Financial Interests, Personal, Full or part-time Employment: Guardant Health Pte. Ltd. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.