Table 4. List of clinical trials that assessed FGFR FISH as a biomarker when evaluating FGFR inhibitor based therapy.

Drug	Treatment regimen	Biomarker	Tumor histology	Criteria for biomarker positivity	Percent of tumor samples expressing the biomarker	Outcome	Reference
Dovitinib	Dovitinib 500 mg/day, for 5 days followed by 2 days off (28 days cycle)	FGFR FISH/ CSH/SISH	Metastatic breast cancer	≥6 copies of FGFR1 classified as positive for FGFR1 amplification	- 28% (23 of 81 patients) FGFR1+, HR+ - 42% (34 of 81 patients) FGFR1-, HR+ - 27% (22 of 81 patients) FGFR1-, HR- - 2.5% (2 of 81 patients) FGFR1+, HR-; treatment arm terminated prior to completion of study enrollment	Median PFS: - FGFR1+, HR+: 3.6 months - FGFR1-, HR+: 3.5 months - FGFR1-, HR-: 2.1 months SD: - FGFR1+, HR+: 45% (9 of 20 patients) - FGFR1-, HR+: 48% (15 of 31 patients) - FGFR1-, HR-: 25% (4 of 16 patients) PD: - FGFR1+, HR+: 25% (5 of 20 patients) - FGFR1-, HR+: 29% (9 of 31 patients) - FGFR1-, HR-: 31% (5 of 16 patients)	[236]
E3810 (Lucitanib)	Lucitanib 20 mg or 15 mg per day	- FGFR1 FISH; Additional biomarkers (as per study design): - FGFR1 CGH array - FGF3 CGH array	Breast cancer	- FGFR1 FISH: ≥6 copies of FGFR1 per nucleus or FGFR1/CEN8 > 2.2 - FGFR1 CGH array: 8p11-12 amplification log2 ratio > 0.9 - FGF3 CGH array: 11q12-14 amplification log2 ratio > 0.9	- 35% (18 of 51 patients) in expansion cohort - 12 breast cancer patients positive for FGF	10 breast cancer patients were evaluable for response. - PR: 7 patients; 1 additional case exhibited response in bone lesions on PET scan - SD: 1 patient - PD: 2 patients	[193]

Abbreviations: FGFR: Fibroblast growth factor receptor; CISH: Chromogenic in situ hybridization; SISH: Silver in situ hybridization; FISH, fluorescent in situ hybridization; FGFR1: Fibroblast growth factor receptor 1; HR: Hormone receptor; PFS, progression free survival; SD: Stable disease; PD: Progressive disease; PR, partial response; CGH: Comparative genomic hybridization; FGF3: Fibroblast growth factor 3.