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e-Posters

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

Date

06 Oct 2021

Session

e-Posters

Presenters

Raphael Ari

Citation

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

Authors

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
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Abstract 15P

Background

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.

Methods

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.

Results

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

Conclusions

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.

Funding

Has not received any funding.

Disclosure

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.

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