Journal Article

Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma

Arlene O, Siefker-Radtke, Ben, Tran, Severine, Banek, Sydney, Akapame, Nobuaki, Matsubara, Robert A, Huddart, Spyros, Triantos, Sutapa, Mukhopadhyay, Nicole L, Stone, Yohann, Loriot, Earle F, Burgess, Begoña P, Valderrama, Yin, Kean, Ja Hyeon, Ku, Arlene, Siefker-Radtke, Valentina, Guadalupi, Kris, Deprince, Se Hoon, Park, Nadine, Houede

2023

Overview

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.).

• Publisher: Massachusetts Medical Society
• Subject: [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