دورية أكاديمية
Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma.
| العنوان: | Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma. |
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| المؤلفون: | Loriot, Y, Necchi, A, Park, SH, Garcia-Donas, J, Huddart, R, Burgess, E, Fleming, M, Rezazadeh, A, Mellado, B, Varlamov, S, Joshi, M, Duran, I, Tagawa, ST, Zakharia, Y, Zhong, B, Stuyckens, K, Santiago-Walker, A, De Porre, P, O'Hagan, A, Avadhani, A, Siefker-Radtke, AO, BLC2001 Study Group |
| المساهمون: | Huddart, Robert |
| بيانات النشر: | MASSACHUSETTS MEDICAL SOC |
| سنة النشر: | 2019 |
| المجموعة: | The Institute of Cancer Research (ICR): Publications Repository |
| مصطلحات موضوعية: | BLC2001 Study Group, Urothelium, Humans, Urologic Neoplasms, Neoplasm Metastasis, Pyrazoles, Quinoxalines, Receptors, Fibroblast Growth Factor, Antineoplastic Agents, Protein Kinase Inhibitors, Treatment Outcome, Mutation, Adult, Aged, 80 and over, Middle Aged, Protein-Tyrosine Kinases, Kaplan-Meier Estimate, Progression-Free Survival |
| الوصف: | BACKGROUND: Alterations in the gene encoding fibroblast growth factor receptor (FGFR) are common in urothelial carcinoma and may be associated with lower sensitivity to immune interventions. Erdafitinib, a tyrosine kinase inhibitor of FGFR1-4, has shown antitumor activity in preclinical models and in a phase 1 study involving patients with FGFR alterations. METHODS: In this open-label, phase 2 study, we enrolled patients who had locally advanced and unresectable or metastatic urothelial carcinoma with prespecified FGFR alterations. All the patients had a history of disease progression during or after at least one course of chemotherapy or within 12 months after neoadjuvant or adjuvant chemotherapy. Prior immunotherapy was allowed. We initially randomly assigned the patients to receive erdafitinib in either an intermittent or a continuous regimen in the dose-selection phase of the study. On the basis of an interim analysis, the starting dose was set at 8 mg per day in a continuous regimen (selected-regimen group), with provision for a pharmacodynamically guided dose escalation to 9 mg. The primary end point was the objective response rate. Key secondary end points included progression-free survival, duration of response, and overall survival. RESULTS: A total of 99 patients in the selected-regimen group received a median of five cycles of erdafitinib. Of these patients, 43% had received at least two previous courses of treatment, 79% had visceral metastases, and 53% had a creatinine clearance of less than 60 ml per minute. The rate of confirmed response to erdafitinib therapy was 40% (3% with a complete response and 37% with a partial response). Among the 22 patients who had undergone previous immunotherapy, the confirmed response rate was 59%. The median duration of progression-free survival was 5.5 months, and the median duration of overall survival was 13.8 months. Treatment-related adverse events of grade 3 or higher, which were managed mainly by dose adjustments, were reported in 46% of the patients; 13% of ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print; 348; application/pdf |
| اللغة: | English |
| تدمد: | 0028-4793 1533-4406 |
| العلاقة: | The New England journal of medicine, 2019, 381 (4), pp. 338 - 348; https://repository.icr.ac.uk/handle/internal/3325Test |
| DOI: | 10.1056/nejmoa1817323 |
| الإتاحة: | https://doi.org/10.1056/nejmoa1817323Test https://repository.icr.ac.uk/handle/internal/3325Test |
| حقوق: | https://www.rioxx.net/licenses/under-embargo-all-rights-reservedTest |
| رقم الانضمام: | edsbas.5E57B9B7 |
| قاعدة البيانات: | BASE |
| تدمد: | 00284793 15334406 |
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| DOI: | 10.1056/nejmoa1817323 |