Erdafitinib in Asian patients with advanced solid tumors: an open-label, single-arm, phase IIa trial

• Published in: BMC cancer Vol. 24; no. 1; pp. 1006 - 13
• Main Authors: Park, Joon Oh, Feng, Yin-Hsun, Su, Wu-Chou, Oh, Do-Youn, Keam, Bhumsuk, Shen, Lin, Kim, Sang-We, Liu, Xiufeng, Liao, Huimin, Qing, Min, Zhang, Chong, Qian, Jiaqi, Tang, Xiaodan, Li, Peng, Triantos, Spyros, Sweiti, Hussein
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 13.08.2024; BioMed Central; BMC
• Subjects: Adult; Adverse events; Aged; Aged, 80 and over; Asian patients; Asian People; Asians; Bile Duct Neoplasms - drug therapy; Bile Duct Neoplasms - pathology; Brain tumors; Cancer; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Chemotherapy; Cholangiocarcinoma; Cholangiocarcinoma - drug therapy; Cholangiocarcinoma - genetics; Cholangiocarcinoma - pathology; Clinical trials; Consent; Disease control; Drug dosages; Drug therapy; Drug withdrawal; Erdafitinib; Esophageal cancer; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Esophagus; FDA approval; Female; FGFR inhibitor; Fibroblast growth factor receptors; Genetic aspects; Gliomas; Growth factors; Health aspects; Humans; Hyperphosphatemia; Kinases; Liver cancer; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Metastasis; Middle Aged; Mortality; Mutation; Non-small cell lung carcinoma; NSCLC; Patient outcomes; Pharmacokinetics; Progression-Free Survival; Pyrazoles - administration & dosage; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Quinoxalines - administration & dosage; Quinoxalines - adverse effects; Quinoxalines - therapeutic use; Receptors, Fibroblast Growth Factor - antagonists & inhibitors; Receptors, Fibroblast Growth Factor - genetics; Small cell lung carcinoma; Solid tumors; Thorax; Titration; Toxicity; Tumors; Asia; East Asia; China; FGFR inhibitor; NSCLC; Asian patients; Cholangiocarcinoma; Erdafitinib
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-024-12584-0

FGFR genomic aberrations occur in approximately 5-10% of human cancers. Erdafitinib has previously demonstrated efficacy and safety in FGFR-altered advanced solid tumors, such as gliomas, thoracic, gastrointestinal, gynecological, and other rare cancers. However, its efficacy and safety in Asian patients remain largely unknown. We conducted a multicenter, open-label, single-arm phase IIa study of erdafitinib to evaluate its efficacy in Asian patients with FGFR-altered advanced cholangiocarcinoma, non-small cell lung cancer (NSCLC), and esophageal cancer. Patients with pathologically/cytologically confirmed, advanced, or refractory tumors who met molecular and study eligibility criteria received oral erdafitinib 8 mg once daily with an option for pharmacodynamically guided up-titration to 9 mg on a 28-day cycle, except for four NSCLC patients who received erdafitinib 10 mg (7 days on/7 days off) as they were recruited before the protocol amendment. The primary endpoint was investigator-assessed objective response rate per RECIST v1.1. Secondary endpoints included progression-free survival, duration of response, disease control rate, overall survival, safety, and pharmacokinetics. Thirty-five patients (cholangiocarcinoma: 22; NSCLC: 12; esophageal cancer: 1) were enrolled. At data cutoff (November 19, 2021), the objective response rate for patients with cholangiocarcinoma was 40.9% (95% CI, 20.7-63.6); the median progression-free survival was 5.6 months (95% CI, 3.6-12.7) and median overall survival was 40.2 months (95% CI, 12.4-not estimable). No patient with RET/FGFR-altered NSCLC achieved objective response and the disease control rate was 25.0% (95% CI, 5.5-57.2%), with three patients with stable disease. The single patient with esophageal cancer achieved partial response. All patients experienced treatment-emergent adverse events, and grade ≥ 3 treatment-emergent adverse events were reported in 22 (62.9%) patients. Hyperphosphatemia was the most frequently reported treatment-emergent adverse event (all-grade, 85.7%). Erdafitinib demonstrated efficacy in a population of Asian patients in selected advanced solid tumors, particularly in those with advanced FGFR-altered cholangiocarcinoma. Treatment was tolerable with no new safety signals. This trial is registered with ClinicalTrials.gov (NCT02699606); study registration (first posted): 04/03/2016.