5528 - Genomic and clinical characterization of Non-small cell lung cancer (NSCLC) patients harboring mutations in FGFR2 and FGFR3

Background

Amplifications in FGFR1are a potential target to therapy with FGFR inhibitors in squamous cell carcinoma NSCLC (SqCC). Recent insights in other entities demonstrate that the efficacy of these inhibitors is not limited to FGFR1 but affects the whole receptor family. We set out this analysis to identify NSCLC patients with mutations in FGFR2 and/or FGFR3 and to describe clinical and genomic characteristics.

Methods

Within the Network Genomic Medicine Lung Cancer (NGM), all stage IV patients underwent genomic testing using a gene panel consistent of 17 potential oncogenes. The panel was implemented in 2015, and data cut-off for this analysis was July 2018. The panel focuses on point mutations or deletions, i. e., rearrangements or copy-number aberrations were not detectable.

Results

Of 6000 patients analyzed, 26 (0.4%) had an FGFR2 mutation and 21 (0.4%) an FGFR3 mutation. 95% of the detected mutations have not been reported so far. Clinically, both subgroups differed from each other, most strikingly in the clinical presentation: The vast majority of FGFR2 mutations were detected in non-SqCC (76.9%), whereas FGFR3 mutations occurred more commonly in SqCC (57.1%). In the FGFR2 group, more female patients were affected (57.7%), contrasting 71.4% male patients in the FGFR3 group. KRAS mutations co-occurred more frequently in the FGFR2 group (23.1% vs 9.5%) and PIK3CA mutations more frequently in the FGFR3 group (19.0% vs 7.7%). For both groups, most mutations did not affect the kinase domain. Patients with FGFR2 mutation seem to have a favorable outcome as compared to FGFR3 patients (median overall survival not reached vs 8.0 months), but follow-up is still immature (p = 0.201).

Conclusions

Patients with FGFR2 and FGFR3 mutations represent two vastly different subgroups of NSCLC patients. Both mutations are not limited to SqCC and seem to have different prognoses for the outcome of the patients. Further work on the characterization of the different mutations is ongoing.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Network Genomic Medicine (NGM) Lung Cancer.

Funding

Has not received any funding.

Disclosure

M. Scheffler: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy, Travel / Accommodation / Expenses: Mediolanum Biosciences; Honoraria (self): Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Takeda; Advisory / Consultancy: BMS. A. Kron: Advisory / Consultancy: BMS; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Novartis. D.S.Y. Abdulla: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Travel / Accommodation / Expenses: AbbVie. R. Riedel: Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly. S. Michels: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Boehringer Ingelheim. R.N. Fischer: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Travel / Accommodation / Expenses: Boehringer Ingelheim. S. Merkelbach-Bruse: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Novartis. R. Büttner: Honoraria (self): Pfizer; Honoraria (self): Novartis. L. Nogova: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD. J. Wolf: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AbbVie; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Chugai; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Ignyta; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest.