Infigratinib in Early-Line and Salvage Therapy for FGFR3-Altered Metastatic Urothelial Carcinoma
| Autor: | Daniel P. Petrylak, Cindy Xu, Corina Andresen, Ulka N. Vaishampayan, Jessica Rearden, Howard A. Burris, Jean H. Hoffman-Censits, Ugo De Giorgi, Sumanta K. Pal, Sumati Gupta, Jonathan E. Rosenberg, Dean F. Bajorin, Yung Lyou, Ai Li, Siamak Daneshmand, David I. Quinn, Petros Grivas, Susan Moran, Matthew D. Galsky |
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| Rok vydání: | 2022 |
| Předmět: |
Male
medicine.medical_specialty Metastatic Urothelial Carcinoma medicine.drug_class Urology medicine.medical_treatment Salvage therapy Subgroup analysis Gastroenterology Tyrosine-kinase inhibitor Internal medicine medicine Clinical endpoint Humans Receptor Fibroblast Growth Factor Type 3 Platinum Salvage Therapy Carcinoma Transitional Cell Chemotherapy Bladder cancer business.industry Phenylurea Compounds medicine.disease Primary tumor Pyrimidines Urinary Bladder Neoplasms Oncology Female business |
| Zdroj: | Clinical Genitourinary Cancer. 20:35-42 |
| ISSN: | 1558-7673 |
| DOI: | 10.1016/j.clgc.2021.10.004 |
| Popis: | Introduction To describe the efficacy of infigratinib, a potent, selective fibroblast growth factor receptor (FGFR) 1-3 tyrosine kinase inhibitor, across lines of therapy (LOT) in patients with metastatic urothelial cancer (mUC). Patients and Methods Eligible patients had mUC and prior platinum-based chemotherapy, unless contraindicated, and activating FGFR3 mutation/fusion. Patients received infigratinib 125 mg orally daily (3 weeks on/1 week off) in a single-arm, open-label study. Primary endpoint: investigator-assessed confirmed objective response rate (ORR). Disease control rate (DCR), progression-free survival (PFS), best overall response (BOR) that included unconfirmed responses, and overall survival (OS) were also assessed. Subgroup analysis of efficacy and safety outcomes by LOT was performed. Results Sixty-seven patients were enrolled; 13 (19.4%) received infigratinib as early-line therapy for mUC due to ineligibility to receive platinum-based chemotherapy. Overall, ORR was 25.4% (95% CI 15.5-37.5) and DCR was 64.2% (95% CI 51.5-75.5). ORR was 30.8% (95% CI 9.1-61.4) with early-line infigratinib and 24.1% (95% CI 13.5-37.6) for ≥2 LOT. DCR was 46.2% (95% CI 19.2-74.9) for early-line and 68.5% (95% CI 54.4-80.5) for ≥2 LOT. PFS and OS appeared similar in both groups. Thirteen of 59 patients with a bladder primary tumor received early-line treatment with an ORR of 30.5% (95% CI 9.1-61.4), and 46 received ≥2 LOT with an ORR of 20.3% (95% CI 9.4-33.9); BOR was 38.5% (95% CI: 13.9-68.4%) and 42.6% (95% CI: 29.2-56.8%) in the early-line and salvage settings, respectively. Eight patients with upper tract urothelial carcinoma received salvage therapy (ORR, 50.0%; DCR, 100.0%). No significant differences in toxicities between LOT were observed. Conclusion Infigratinib has notable activity in patients with mUC regardless of LOT. The findings support the evaluation of infigratinib across different settings in mUC. |
| Databáze: | OpenAIRE |
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