Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma

• Published in: New England Journal of Medicine Vol. 389; no. 21; pp. 1961 - 1971
• Main Authors: Yohann, Loriot, Nobuaki, Matsubara, Se Hoon, Park, Robert A, Huddart, Earle F, Burgess, Nadine, Houede, Severine, Banek, Valentina, Guadalupi, Ja Hyeon, Ku, Begoña P, Valderrama, Ben, Tran, Spyros, Triantos, Yin, Kean, Sydney, Akapame, Kris, Deprince, Sutapa, Mukhopadhyay, Nicole L, Stone, Arlene O, Siefker-Radtke, Arlene, Siefker-Radtke
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 23.11.2023
• Subjects: [SDV]Life Sciences [q-bio]; Adult; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; Cancer therapies; Carcinoma, Transitional Cell; Carcinoma, Transitional Cell - drug therapy; Carcinoma, Transitional Cell - mortality; Carcinoma, Transitional Cell - pathology; Cell death; Chemotherapy; Confidence intervals; Docetaxel; Docetaxel - adverse effects; Docetaxel - therapeutic use; Fibroblast growth factor receptors; Humans; Immune Checkpoint Inhibitors; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; Kinases; Life Sciences; Metastases; Metastasis; Mutation; Patients; PD-1 protein; PD-L1 protein; Receptors, Fibroblast Growth Factor; Receptors, Fibroblast Growth Factor - antagonists & inhibitors; Tumors; Urinary Bladder Neoplasms; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - mortality; Urinary Bladder Neoplasms - pathology; Urological cancer; Urothelial carcinoma; North America; Europe
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/nejmoa2308849

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 alterations who have progression after platinum-containing chemotherapy. The effects of erdafitinib in patients with -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 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 alterations after previous anti-PD-1 or anti-PD-L1 treatment. (Funded by Janssen Research and Development; THOR ClinicalTrials.gov number, NCT03390504.).