Table 2.
Methods used in clinical trials to identify patients for FGFR inhibitor treatment.
| Technology | Pros | Cons | Patient Population * | Prevalence |
|---|---|---|---|---|
| FGFR protein expression | ||||
| Immunohistochemistry | Broadly available, direct measure of receptor expression, keeps spatial resolution, short TAT | No single antibody, needs multiplexing for pan-FGFR inhibitors, Requires pathologist training or central testing | FGFR2b + gastric cancer | 30% |
| FGFR mRNA expression | ||||
| PCR | Sensitive, cheap, short TAT Easy to establish for each FGFR subtype |
No preservation of spatial resolution | FGFR4 + HCC pts (Roblitinib) | Unknown |
| Nanostring | Sensitive, highly multiplex testing | Expensive, tumor content needs to be retrospectively calculated | FGFR1/2/3 + all comers (Rogaratinib) FGFR2 + gastric cancer (AZD4547) |
Up to 25% Unknown |
| RNA-ISH | Sensitive, keeps spatial resolution, IHC-like workflow, short TAT, multiplex possible | Requires pathologist training or central testing | FGFR1/2/3 + all comers (Rogaratinib) FGFR1&3 + urothelial cancer patients (Rogaratinib) |
25% |
| RNAseq | Sensitive, highly multiplex testing |
Expensive, long TAT (several weeks), no preservation of spatial resolution, | Not applied in any FGFR inhibitor trial to date | Unknown |
| FGFR DNA alterations | ||||
| FISH | Keeps spatial resolution | Requires fluorescence microscopy, multiplex possible |
FGFR2 + gastric cancer (AZD4547) | 4–7% [11] |
| PCR | Short TAT (7 days) | No preservation of spatial resolution | FGFR2&3 fusion and FGFR3 mutations in urothelial carcinoma (QIAGEN’s FDA approved CDx therascreen® FGFR kit for Erdafitinib) | 20% [7] |
| NGS | Highly multiplex testing | Expensive, long TAT, no preservation of spatial resolution | FGFR2 fusion-positive iCCA (Foundation One™ as FDA approved CDx for Pemigatinib & Infigratinib) | 10% [91,98] |
| FGF ligand | ||||
| IHC | Broadly available, direct measure of receptor expression, keeps spatial resolution, short TAT | No single antibody, needs multiplexing for pan-FGFR inhibitors, Requires pathologist training or central testing | FGF-19 serum levels in HCC (Fisogatinib) | 27% [32] |
CDx: Companion diagnostics; FDA: Food and Drug Administration; FISH: fluorescence in situ hybridization; HCC: hepatocellular carcinoma; iCCA: intrahepatic cholangiocellular carcinoma: IHC: immunohistochemistry; NGS: next generation sequencing; PCR: polymerase chain reaction; RNA-ISH: RNA in situ hybridization; RNA-seq: RNA sequencing; TAT: turnaround time. * Only patient populations that have been enrolled into FGFR inhibitor trials.