دورية أكاديمية
Erdafitinib in Asian patients with advanced solid tumors: an open-label, single-arm, phase IIa trial.
العنوان: | Erdafitinib in Asian patients with advanced solid tumors: an open-label, single-arm, phase IIa trial. |
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المؤلفون: | Park JO; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Korea. oncopark@skku.edu., Feng YH; Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan., Su WC; Department of Oncology, National Cheng Kung University Hospital, Tainan, Taiwan., Oh DY; Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea., Keam B; Department of Internal Medicine, Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea., Shen L; Department of GI Oncology, Peking University Cancer Hospital & Institute, Beijing, China., Kim SW; Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea., Liu X; Qinhuai Medical Zone, Eastern Theater General Hospital of the Chinese PLA, Nanjing, China., Liao H; Janssen China R&D Center, Shanghai, China., Qing M; Janssen China R&D Center, Shanghai, China., Zhang C; Janssen China R&D Center, Shanghai, China., Qian J; Janssen China R&D Center, Shanghai, China., Tang X; Janssen China R&D Center, Shanghai, China., Li P; Janssen China R&D Center, Shanghai, China., Triantos S; Oncology Clinical Development, Janssen R&D, PA, USA., Sweiti H; Oncology Clinical Development, Janssen R&D, PA, USA. |
المصدر: | BMC cancer [BMC Cancer] 2024 Aug 13; Vol. 24 (1), pp. 1006. Date of Electronic Publication: 2024 Aug 13. |
نوع المنشور: | Journal Article; Clinical Trial, Phase II; Multicenter Study |
اللغة: | English |
بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 100967800 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2407 (Electronic) Linking ISSN: 14712407 NLM ISO Abbreviation: BMC Cancer Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : BioMed Central, [2001- |
مواضيع طبية MeSH: | Cholangiocarcinoma*/drug therapy , Cholangiocarcinoma*/genetics , Cholangiocarcinoma*/pathology , Carcinoma, Non-Small-Cell Lung*/drug therapy , Carcinoma, Non-Small-Cell Lung*/genetics , Carcinoma, Non-Small-Cell Lung*/pathology , Pyrazoles*/therapeutic use , Pyrazoles*/administration & dosage , Pyrazoles*/adverse effects, Humans ; Female ; Male ; Middle Aged ; Aged ; Adult ; Quinoxalines/therapeutic use ; Quinoxalines/administration & dosage ; Quinoxalines/adverse effects ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Esophageal Neoplasms/drug therapy ; Esophageal Neoplasms/pathology ; Esophageal Neoplasms/genetics ; Receptors, Fibroblast Growth Factor/antagonists & inhibitors ; Receptors, Fibroblast Growth Factor/genetics ; Asian People ; Bile Duct Neoplasms/drug therapy ; Bile Duct Neoplasms/pathology ; Progression-Free Survival ; Aged, 80 and over |
مستخلص: | Background: 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. Methods: 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. Results: 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%). Conclusions: 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. Trial Registration: This trial is registered with ClinicalTrials.gov (NCT02699606); study registration (first posted): 04/03/2016. (© 2024. The Author(s).) |
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فهرسة مساهمة: | Keywords: Asian patients; Cholangiocarcinoma; Erdafitinib; FGFR inhibitor; NSCLC |
سلسلة جزيئية: | ClinicalTrials.gov NCT02699606 |
المشرفين على المادة: | 890E37NHMV (erdafitinib) 0 (Pyrazoles) 0 (Quinoxalines) 0 (Receptors, Fibroblast Growth Factor) |
تواريخ الأحداث: | Date Created: 20240813 Date Completed: 20240813 Latest Revision: 20240816 |
رمز التحديث: | 20240816 |
مُعرف محوري في PubMed: | PMC11323360 |
DOI: | 10.1186/s12885-024-12584-0 |
PMID: | 39138436 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1471-2407 |
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DOI: | 10.1186/s12885-024-12584-0 |