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|
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.