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gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pemigatinib-cholangiocarcinoma-fgfr2-rearrangement gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-infigratinib-metastatic-cholangiocarcinoma biliary tract cancer month download article/chapter fgfr2 fusion-positive cholangiocarcinoma fgfr-altered advanced cholangiocarcinoma atp-competitive fgfr inhibitors solid tumors harboring infigratinib approval letter fgfr-altered cca diagnosed abou-alfa kg oral pan-fgfr inhibitor pemigatinib approval letter comprehensive molecular profiling fgfr2 genomic aberrations fgfr2-fusion cholangiocarcinoma fgfr2 gene fusion cancer treat rev mol cancer ther polyclonal acquired resistance sporadic intrahepatic cholangiocarcinoma full article pdf privacy choices/manage cookies wen wee ma related subjects drugs amit mahipal declare advanced solid tumours fgfr gene fusion health grant p30ca15083 clin cancer res fgfr genetic aberrations health sciences research harboring fgfr alterations fgfr2 fusions curr opin gastroenterol lowery metastatic cholangiocarcinoma metastatic cca patients irreversible fgfr1–4 inhibitor fgfr signaling pathway european economic area kaplan-meier method el-rayes bf droz dit busset fgfr inhibitor therapy small molecule inhibitors including subsequent fgfri conditions privacy policy ethics declarations funding

Questions {❓}

• Targeting the FGFR signaling pathway in cholangiocarcinoma: promise or delusion?

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         headline:Outcomes following FGFR Inhibitor Therapy in Patients with Cholangiocarcinoma
         description:Sequencing efforts in patients with cholangiocarcinoma (CCA) have provided insights into molecular mechanisms including fibroblast growth factor receptor (FGFR) alterations. There is a lack of data on outcomes of patients following cessation of FGFR inhibitor (FGFRi) therapy. We describe the clinical outcomes following initial FGFRi treatment in CCA harboring FGFR alterations. We conducted a multicentric, retrospective analysis of patients with FGFR-altered CCA diagnosed between 2010 and 2021. Median overall survival (OS) and progression-free survival (PFS) analyses were performed using the Kaplan-Meier method. We identified 88 advanced or metastatic CCA patients, 28 males (31.8%) and 60 females (68.2%), harboring FGFR alterations who received FGFRi. Median PFS on initial FGFRi was 6.6 months (95% confidence interval (CI): 5.5–8.3). Following cessation of first FGFRi therapy, 55% patients received systemic therapy as next line: 67% received chemotherapy or targeted treatment and 33% received another FGFRi. Median PFS for patients who received chemotherapy or targeted agent was 2.1 months (95% CI 1.6–5.7) and for patients who received a second FGFRi was 3.7 months (95% CI 1.5–not evaluable). OS was 2.0 months for patients who did not receive any therapy compared to 8.7 months with chemotherapy and 8.6 months with another FGFRi. In addition, one patient treated with pemigatinib developed FGFR2 M540_I541insMM alteration at time of resistance, which has not been functionally characterized and its effect on protein function remains unknown. Understanding the mechanisms of resistance with FGFRi is essential to understand sequencing of treatments. In this study, patients received standard chemotherapy in the first line and were fit enough to be considered for subsequent therapy with an FGFRi. Almost half of the patients become ineligible to receive further systemic therapy following progression on FGFRi. As more agents are being introduced, detailed understanding of outcomes following treatment with an FGFRi, including subsequent FGFRi, is essential.
         datePublished:2022-09-02T00:00:00Z
         dateModified:2022-09-02T00:00:00Z
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      headline:Outcomes following FGFR Inhibitor Therapy in Patients with Cholangiocarcinoma
      description:Sequencing efforts in patients with cholangiocarcinoma (CCA) have provided insights into molecular mechanisms including fibroblast growth factor receptor (FGFR) alterations. There is a lack of data on outcomes of patients following cessation of FGFR inhibitor (FGFRi) therapy. We describe the clinical outcomes following initial FGFRi treatment in CCA harboring FGFR alterations. We conducted a multicentric, retrospective analysis of patients with FGFR-altered CCA diagnosed between 2010 and 2021. Median overall survival (OS) and progression-free survival (PFS) analyses were performed using the Kaplan-Meier method. We identified 88 advanced or metastatic CCA patients, 28 males (31.8%) and 60 females (68.2%), harboring FGFR alterations who received FGFRi. Median PFS on initial FGFRi was 6.6 months (95% confidence interval (CI): 5.5–8.3). Following cessation of first FGFRi therapy, 55% patients received systemic therapy as next line: 67% received chemotherapy or targeted treatment and 33% received another FGFRi. Median PFS for patients who received chemotherapy or targeted agent was 2.1 months (95% CI 1.6–5.7) and for patients who received a second FGFRi was 3.7 months (95% CI 1.5–not evaluable). OS was 2.0 months for patients who did not receive any therapy compared to 8.7 months with chemotherapy and 8.6 months with another FGFRi. In addition, one patient treated with pemigatinib developed FGFR2 M540_I541insMM alteration at time of resistance, which has not been functionally characterized and its effect on protein function remains unknown. Understanding the mechanisms of resistance with FGFRi is essential to understand sequencing of treatments. In this study, patients received standard chemotherapy in the first line and were fit enough to be considered for subsequent therapy with an FGFRi. Almost half of the patients become ineligible to receive further systemic therapy following progression on FGFRi. As more agents are being introduced, detailed understanding of outcomes following treatment with an FGFRi, including subsequent FGFRi, is essential.
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Analytics and Tracking {📊}

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Libraries {📚}

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CDN Services {📦}

• Crossref