Table 2.
FGFR targeted therapies in clinical trial and case studies in paediatric and young adult cancer.
| Drug | Targets | Trial | Tumour types | Response rate | Refs |
|---|---|---|---|---|---|
| Multi-kinase inhibitors | |||||
| Regorafenib | FGFR1, RET, VEGFR, KIT, PDGFR |
SARCO24 (Phase II, NCT02048371) |
Advanced liposarcoma, osteogenic sarcoma, rhabdomyosarcoma, and Ewing family sarcoma (≥10 years of age) |
Osteosarcoma: Median PFS 3.6 months (vs. 1.7 months control) Ewing sarcoma: Median PFS 3.4 months |
[112], [116] |
| REGOBONE (Phase II, NCT02389244) |
Metastatic bone sarcomas: conventional high-grade osteosarcoma, Ewing sarcoma of bone, intermediate or high-grade chondrosarcomas and chordomas and either bone or soft tissue metastatic CIC-rearranged sarcomas (≥10 years of age) |
Osteosarcoma: 8-week non-progressive disease 65% (17/26 patients); 2 PR and 15 SD Median PFS 3.8 months (vs. 0.9 months control) Ewing sarcoma: 8-week non-progressive disease 57% (13/23 patients); 5 PR and 8 SD Median PFS 2.6 months (vs. 0.9 months control) |
[113], [115] | ||
| FaR-RMS (Phase I/II, NCT04625907) | Children and adolescents with newly diagnosed rhabdomyosarcoma | Recruiting, response data yet to be reported | NA | ||
|
SARC038 (Phase II, NCT04803877) |
Combination of regorafenib and with nivolumab in patients with refractory or recurrent osteosarcoma (≥5 years of age) |
Active, not recruiting | NA | ||
| Sorafenib | FGFR1, RAF, VEGFR, KIT, PDGFR, FLT3 |
Phase II |
Relapsed and unresectable high-grade osteosarcoma (≥14 years of age) | 4-month PFS 46% (n = 35); median PFS 4-months; OS 7-months; 3 PR, 2 MR, 12 SD | [114] |
| Lenvatinib | FGFR1/2/3/4, RET, VEGFR, PDGFR, KIT |
Phase II |
Relapsed/ refractory osteosarcoma (aged 2-25 years) |
Monotherapy: 4-month PFS 29%; median PFS 3-months; ORR 6.7%; 2 PR and 13 SD Lenvatinib + etoposide/ifosfamide: 4-month PFS 51%; median PFS 8.7-months; ORR 9% |
[117], [118] |
| Surufatinib | FGFR1, CSF1R, VEGFR1/2/3 | Phase I/II (NCT05093322) | Paediatric, adolescent, and young adults with relapsed and refractory solid tumours with known or expected dysfunction in VEGFR1/2/3, CSF1R or FGFR1 | Active, not recruiting | NA |
| Ponatinib | FGFR1/2/3/4, CSF1R, PDGFR, VEGFR1/3, RET | Case report |
FGFR3-PHGDH oligodendroglioma (10 years) |
Partial response, sustained for 7 months at time of reporting | [119] |
| FGFR-selective inhibitors | |||||
| Erdafitinib | FGFR1/2/3/4 | NCI-COG- Paediatric MATCH trial (Phase II, NCT03155620) | Paediatric (1–21 years) relapsed or refractory solid tumours, non-Hodgkin lymphoma, or histiocytic disorders with identified FGFR mutations | Currently recruiting; response data yet to be reported (n = 131 patients enroled in a treatment arm; # in arm B (erdafitinib) not disclosed) | [41] |
| RAGNAR study (Phase II, NCT04083976) |
Paediatric patients with advanced solid tumours with FGFR gene alterations (6-18 years) |
Recruiting, response data yet to be reported | [126] | ||
| Case report |
FGFR1-EBF2 fusion positive-spindle and round cell neoplasm (9-months) |
Considerable reduction in tumour size following 12-week treatment (no longer tender to palpation). Treatment ongoing at time of report. | [42] | ||
| Debio1347 | FGFR1/2/3 | Single centre study (MSKCC) with patients treated under single patient use protocols |
Paediatric Patients With Recurrent or Refractory FGFR-Altered Gliomas (13-months-14 years) |
4/5 patients were evaluable (3 x LGG and 1 x HGG); 2 PR and 2 SD | [124] |
| Pemigatinib | FGFR1/2/3/4 | Case report (patient enroled in FIGHT-101 (NCT02393248)) | FGFR1 N546K mutant juvenile pilocytic astrocytoma (32-year-old male; first diagnosed with PA at 13 years of age) | Partial response (91% reduction in tumour size as best response over 18 months of sustained response) | [125] |
For studies where a molecular indication was part of the inclusion criteria, the aberration is bolded. All other studies were performed on unselected patients.
PFS progression free survival, OS overall survival, ORR overall response rate, PR partial response, MR minor response, SD stable disease.