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

التفاصيل البيبلوغرافية
العنوان: Erdafitinib in Asian patients with advanced solid tumors: an open-label, single-arm, phase IIa trial.
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
الوصف
تدمد:1471-2407
DOI:10.1186/s12885-024-12584-0