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| Ref Type | Journal Article | ||||||||||||
| PMID | (37870920) | ||||||||||||
| Authors | Loriot Y, Matsubara N, Park SH, Huddart RA, Burgess EF, Houede N, Banek S, Guadalupi V, Ku JH, Valderrama BP, Tran B, Triantos S, Kean Y, Akapame S, Deprince K, Mukhopadhyay S, Stone NL, Siefker-Radtke AO, THOR Cohort 1 Investigators | ||||||||||||
| Title | Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma. | ||||||||||||
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| Abstract Text | Erdafitinib is a pan-fibroblast growth factor receptor (FGFR) inhibitor approved for the treatment of locally advanced or metastatic urothelial carcinoma in adults with susceptible FGFR3/2 alterations who have progression after platinum-containing chemotherapy. The effects of erdafitinib in patients with FGFR-altered metastatic urothelial carcinoma who have progression during or after treatment with checkpoint inhibitors (anti-programmed cell death protein 1 [PD-1] or anti-programmed death ligand 1 [PD-L1] agents) are unclear.We conducted a global phase 3 trial of erdafitinib as compared with chemotherapy in patients with metastatic urothelial carcinoma with susceptible FGFR3/2 alterations who had progression after one or two previous treatments that included an anti-PD-1 or anti-PD-L1. Patients were randomly assigned in a 1:1 ratio to receive erdafitinib or the investigator's choice of chemotherapy (docetaxel or vinflunine). The primary end point was overall survival.A total of 266 patients underwent randomization: 136 to the erdafitinib group and 130 to the chemotherapy group. The median follow-up was 15.9 months. The median overall survival was significantly longer with erdafitinib than with chemotherapy (12.1 months vs. 7.8 months; hazard ratio for death, 0.64; 95% confidence interval [CI], 0.47 to 0.88; P = 0.005). The median progression-free survival was also longer with erdafitinib than with chemotherapy (5.6 months vs. 2.7 months; hazard ratio for progression or death, 0.58; 95% CI, 0.44 to 0.78; P<0.001). The incidence of grade 3 or 4 treatment-related adverse events was similar in the two groups (45.9% in the erdafitinib group and 46.4% in the chemotherapy group). Treatment-related adverse events that led to death were less common with erdafitinib than with chemotherapy (in 0.7% vs. 5.4% of patients).Erdafitinib therapy resulted in significantly longer overall survival than chemotherapy among patients with metastatic urothelial carcinoma and FGFR alterations after previous anti-PD-1 or anti-PD-L1 treatment. (Funded by Janssen Research and Development; THOR ClinicalTrials.gov number, NCT03390504.). | ||||||||||||
| Molecular Profile | Treatment Approach |
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| Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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| Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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| Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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| FGFR3 R248C | transitional cell carcinoma | sensitive | Erdafitinib | Phase III | Actionable | In a Phase III trial (THOR), Balversa (erdafitinib) therapy improved median overall survival (12.1 mo vs 7.8 mo HR=0.64, p=0.0005), median progression-free survival (5.6 mo vs 2.7 mo), and objective response rate (45.6% (62/135, 9 complete (CR), 53 partial responses (PR) vs 11.5% (15/130, 1 CR, 14 PR) compared to chemotherapy in metastatic urothelial carcinoma patients with alterations in FGFR3, including FGFR3 S249C (n=124), Y373C (n=45), R248C (n=25), G370C (n=13), and FGFR3-TACC3 (n=41) (PMID: 37870920). | 37870920 |
| FGFR3 G370C | transitional cell carcinoma | sensitive | Erdafitinib | Phase III | Actionable | In a Phase III trial (THOR), Balversa (erdafitinib) therapy improved median overall survival (12.1 mo vs 7.8 mo HR=0.64, p=0.0005), median progression-free survival (5.6 mo vs 2.7 mo), and objective response rate (45.6% (62/135, 9 complete (CR), 53 partial responses (PR) vs 11.5% (15/130, 1 CR, 14 PR) compared to chemotherapy in metastatic urothelial carcinoma patients with alterations in FGFR3, including FGFR3 S249C (n=124), Y373C (n=45), R248C (n=25), G370C (n=13), and FGFR3-TACC3 (n=41) (PMID: 37870920). | 37870920 |
| FGFR3 S249C | transitional cell carcinoma | sensitive | Erdafitinib | Phase III | Actionable | In a Phase III trial (THOR), Balversa (erdafitinib) therapy improved median overall survival (12.1 mo vs 7.8 mo HR=0.64, p=0.0005), median progression-free survival (5.6 mo vs 2.7 mo), and objective response rate (45.6% (62/135, 9 complete (CR), 53 partial responses (PR) vs 11.5% (15/130, 1 CR, 14 PR) compared to chemotherapy in metastatic urothelial carcinoma patients with alterations in FGFR3, including FGFR3 S249C (n=124), Y373C (n=45), R248C (n=25), G370C (n=13), and FGFR3-TACC3 (n=41) (PMID: 37870920). | 37870920 |
| FGFR3 Y373C | transitional cell carcinoma | sensitive | Erdafitinib | Phase III | Actionable | In a Phase III trial (THOR), Balversa (erdafitinib) therapy improved median overall survival (12.1 mo vs 7.8 mo HR=0.64, p=0.0005), median progression-free survival (5.6 mo vs 2.7 mo), and objective response rate (45.6% (62/135, 9 complete (CR), 53 partial responses (PR) vs 11.5% (15/130, 1 CR, 14 PR) compared to chemotherapy in metastatic urothelial carcinoma patients with alterations in FGFR3, including FGFR3 S249C (n=124), Y373C (n=45), R248C (n=25), G370C (n=13), and FGFR3-TACC3 (n=41) (PMID: 37870920). | 37870920 |