Abstract 116P
Background
Deregulation of FGFR pathway has been proved to increase cells survival and proliferation leading to FDA approval of drugs in urothelial cancer (erdafitinib) and cholangiocarcinoma [CC] (pemigatinib) as well as agnostic indication trials (ongoing). We present our experience profiling multiple cancer types for FGFR alterations and comparison with in silico data.
Methods
We selected patients whose tumors had been profiled by either Foundation One or ArcherDx gene panels, which cover FGFR 1 to 4 mutations [M], fusions [F], among others. We collected information about cancer type, sample origin (primary vs metastatic[M1]), FGFR alterations and clinical significance based on OncoKB database (pathogenic [P] vs variant of unknown significance [VUS]). In order to compare with local results, we selected from cBioPortal the most abundant database per cancer and sample type. Descriptive statistics were used.
Results
From March 2017 to January 2021, we analyzed samples from 342 patients with urothelial (19%), breast (18.1%), glioblastoma (17%), ovarian (11.1%), prostate (10.2%), esophageal and gastric (6.4%) and others (18.3%). 77.8% were primary and 22.4% M1. Focusing on primary tumors, 95.6% were FGFR wild type [WT], 2.3% of alterations were P and 2.2% VUS. However, cBioportal (n= 5551) showed 98.8% WT, 0.6% P and 0.6% VUS. We analyzed the incidence of P FGFR alterations according to histology in our cohort and compared it with cBioportal (Table). Table: 116P
| Gene and histology | Type of alteration | Samples (n=342) | cBioportal (n=5551) |
| FGFR1 glioblastoma | M F | 3.5% 1.7% | 0% 0% |
| FGRF3 urothelial | M F | 28% 2% | 12.8% 1.7% |
| FGFR4 ovarian | M F | 4.2% 0% | 0% 0% |
| FGFR 1-4 other histologies | M F | ≤1% ≤1% | ≤1% ≤1% |
Moreover, cBioportal showed FGFR2 P alterations in CC (1.4% M, 9.2% F) and endometrial carcinoma (9.1% M), that are underrepresented locally.
Conclusions
Most patients do not show a FGFR alteration. Cancers of higher incidence of P are urothelial, ovarian and glioblastoma. Incidence in most of other tumor types is ≤1%. Low frequency of P highlights difficulties for implementing FGFR inhibitor in clinical practice and the urgent need to settle strategies to identify potential candidates.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
B. Mellado: Financial Interests, Personal, Sponsor/Funding: Astellas; Non-Financial Interests, Personal, Sponsor/Funding: Jansen; Non-Financial Interests, Personal, Sponsor/Funding: Sanofi; Non-Financial Interests, Personal, Sponsor/Funding: Roche; Non-Financial Interests, Personal, Sponsor/Funding: BMS; Non-Financial Interests, Personal, Sponsor/Funding: Merk; Non-Financial Interests, Personal, Sponsor/Funding: Pfizer; Financial Interests, Personal, Funding: Bayer. E. Pineda: Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Amgen. L. Gaba Garcia: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Expert Testimony: AstraZeneca; Financial Interests, Personal, Invited Speaker: Clovis oncology; Financial Interests, Personal, Advisory Board: Clovis Oncology; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: PharmaMar. M. Vidal: Financial Interests, Personal, Sponsor/Funding: Pfizer; Financial Interests, Personal, Sponsor/Funding: Novartis; Financial Interests, Personal, Sponsor/Funding: Roche; Financial Interests, Personal, Sponsor/Funding: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Novartis. L. Ferrer: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Kyowa Kirin; Financial Interests, Personal, Sponsor/Funding: Pfizer; Financial Interests, Personal, Sponsor/Funding: Kyowa Kirin. O. Martínez-Sáez: Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Personal, Advisory Board: Roche. N. Basté: Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Biontech; Financial Interests, Personal, Advisory Role: Nanobiotix; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Eisai. L. Mezquita: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Tecnofarma; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Boehringer Ingelheim; Financial Interests, Personal, Sponsor/Funding: Bristol Myers Squibb; Financial Interests, Personal, Sponsor/Funding: Roche; Financial Interests, Personal, Other: International Mentorship Program funded by AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche. A. Prat: Financial Interests, Personal, Invited Speaker, Lecture fees: Amgen; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Amgen; Financial Interests, Institutional, Other, Clinical trials: Amgen; Financial Interests, Institutional, Other, , Contracted research: Astellas; Financial Interests, Personal, Invited Speaker, Lecture fees: BMS; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: BMS; Financial Interests, Institutional, Other, Contracted research: Boehringer; Financial Interests, Institutional, Other, Contracted research: Celgene; Financial Interests, Personal, Invited Speaker, Lecture fees: Contracted research; Financial Interests, Personal, Invited Speaker, Lecture fees: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Guardan Health; Financial Interests, Institutional, Other, Clinical trials: Lilly; Financial Interests, Personal, Advisory Board, Personal, Advisory role/consultancy: Lilly; Financial Interests, Institutional, Other, Contracted research: Medica Scientia inno Research; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: MSD; Financial Interests, Institutional, Invited Speaker, Lecture fees: Nanostring; Financial Interests, Institutional, Other, Contracted research: Nanostring; Financial Interests, Personal, Invited Speaker, Lecture fees: Nanostring; Financial Interests, Institutional, Other, Contracted research: Novartis; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Oncolytics; Financial Interests, Personal, Expert Testimony, Advisory role/consultancy: Peptomyc; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Pfizer; Financial Interests, Institutional, Other, Contracted research: Pfizer; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Puma; Financial Interests, Institutional, Other, Contracted research: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Other, Contracted research: Roche; Financial Interests, Institutional, Other, Clinical trials: Roche; Financial Interests, Institutional, Other, Contracted research: Sysmex Europa GmbH; Financial Interests, Institutional, Other, Clinical trials: Boehringer; Financial Interests, Personal, Member of the Board of Directors, Leadership role: Reveal Genomics SL; Non-Financial Interests, Other, Leadership roles: Patronage committee: Actitud Frente al Cáncer Foundation; Non-Financial Interests, Other, Leadership roles: Patronage committee: SOLTI Foundation. J. Garcia-Corbacho: Financial Interests, Personal, Advisory Board, FGFR inhibitors implementation in clinical practice: Johnson and Johnson Pharmaceutical; Financial Interests, Institutional, Principal Investigator, Participation in clinical trials of the company as PI: Amgen; Financial Interests, Institutional, Principal Investigator, Participation in clinical trials of the company as PI: Astellas; Financial Interests, Institutional, Principal Investigator, Participation in clinical trials of the company as PI: AstraZeneca; Financial Interests, Institutional, Principal Investigator, Participation in clinical trials of the company as PI: Bayer; Financial Interests, Institutional, Principal Investigator, Participation in clinical trials of the company as PI: Boehringer Ingelheim; Financial Interests, Institutional, Principal Investigator, Participation in clinical trials of the company as PI: CytomX; Financial Interests, Institutional, Principal Investigator, Participation in clinical trials of the company as PI: Daichii Sankyo; Financial Interests, Institutional, Principal Investigator, Participation in clinical trials of the company as PI: Incyte; Financial Interests, Institutional, Principal Investigator, Participation in clinical trials of the company as PI: Johnson and Johnson Pharmaceutical; Financial Interests, Institutional, Principal Investigator, Participation in clinical trials of the company as PI: Lilly; Financial Interests, Institutional, Principal Investigator, Participation in clinical trials of the company as PI: Menarini; Financial Interests, Institutional, Principal Investigator, Participation in clinical trials of the company as PI: Merck. All other authors have declared no conflicts of interest.