Table 1.
Summary of FGFR inhibitors with results in urothelial cancer
| Agent(s) and dose | Mechanism of action | Study design | Biomarker and cohort | Response rate | Median OS | Median PFS | Most common toxicity (any grade) |
|---|---|---|---|---|---|---|---|
| Infigratinib (BGJ398); 125 mg/d, 3 wk on/1 wk off | Oral, selective FGFR 1–3 tyrosine kinase inhibitor | Phase I, single arm, open‐label, n = 67 | FGFR3 alteration; metastatic urothelial cancer after 1 or 2 lines of therapy | CR + PR: 25.4%; PD: 23.9%; SD: 50% | 7.75 mo | 3.75 mo | Hyperphosphatemia, elevated creatinine, fatigue, constipation, anemia, decreased appetite |
| Erdafitinib; 8 mg daily with option of dose escalation to 9 mg | Oral, selective, tyrosine kinase inhibitor of FGFR1–4 | Phase II, open‐label, single arm, n = 99 | Susceptible FGFR3 mutation or FGFR2/3 fusions; metastatic urothelial cancer with disease progression on one line of prior platinum‐containing chemotherapy, including within 12 mo of neoadjuvant or adjuvant platinum‐containing chemotherapy | CR + PR: 40%; PD: 18%; SD: 39%; unknown: 2% | 13.8 mo | 5.5 mo | Hyperphosphatemia, stomatitis, diarrhea, dry mouth, decreased appetite, dysgeusia |
| Pemigatinib (INCB054828); 13.5 mg/d on 21‐d cycle (2 wk on/1 wk off) | Selective, potent, oral inhibitor of FGFR1–3 | Phase II, open label, n = 100 | FGFR/FGF alterations; metastatic or unresectable urothelial cancer progression after 1 or more lines of prior therapy or are platinum ineligible | ORR: 25% | N/A | N/A | Diarrhea, alopecia, fatigue, constipation, dry mouth |
| Rogaratinib; 800 mg twice daily | Oral, selective inhibitor of FGFR 1–4 kinase activity | Phase I, open‐label, n = 51 | Overexpression of tumor FGFR 1–3 mRNA; advanced urothelial cancer progression after standard of care treatment | CR + PR: 24%; SD: 49%; PD: 27% | N/A | 100 d | Hyperphosphatemia, diarrhea, decreased appetite |
| Rogaratinib 800 mg twice daily vs. chemotherapy (docetaxel, paclitaxel, or vinflunine); Interim analysis | Oral, selective inhibitor of FGFR 1–4 kinase activity | Phase II/III, randomized, open‐label study, n = 175 | FGFR1–3 mRNA overexpression and/or FGFR3‐activating mutations and/or translocations; metastatic urothelial cancer in patients who received prior platinum chemotherapy | Rogaratinib: CR + PR: 19%; SD: 28%; PD: 31%; chemotherapy: CR + PR: 19%; SD: 35%; PD: 24% | Rogaratinib: 8.3 months (95% CI 6.5, NE); chemotherapy: 9.8 months (95% CI 6.8, NE) | Rogaratinib: 2.7 months (95% CI, 1.6–4.6); chemotherapy: 3.2 months (95% CI, 2.7–4.4); 1‐sided p value = .86) | Rogaratinib: diarrhea, hyperphosphatemia, decreased appetite, nausea. Chemotherapy: constipation, fatigue, anemia, decreased appetite, neutropenia |
Abbreviations: CI, confidence interval; CR, complete response; FGFR, fibroblast growth factor receptor; N/A, not applicable; NE, Not evaluable; ORR, overall response rate; PD, progressive disease; PR, partial response; SD, stable disease.