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Activity and safety of the multi-target tyrosine kinase inhibitor cabozantinib in patients with metastatic gastrointestinal stromal tumour after treatment with imatinib and sunitinib: European Organisation for Research and Treatment of Cancer phase II trial 1317 'CaboGIST'

Identifikátory výsledku

  • Kód výsledku v IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F20%3A10411860" target="_blank" >RIV/00216208:11130/20:10411860 - isvavai.cz</a>

  • Nalezeny alternativní kódy

    RIV/00064203:_____/20:10411860

  • Výsledek na webu

    <a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=JtWnNvITc-" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=JtWnNvITc-</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.ejca.2020.04.021" target="_blank" >10.1016/j.ejca.2020.04.021</a>

Alternativní jazyky

  • Jazyk výsledku

    angličtina

  • Název v původním jazyce

    Activity and safety of the multi-target tyrosine kinase inhibitor cabozantinib in patients with metastatic gastrointestinal stromal tumour after treatment with imatinib and sunitinib: European Organisation for Research and Treatment of Cancer phase II trial 1317 'CaboGIST'

  • Popis výsledku v původním jazyce

    Background: Gastrointestinal stromal tumour (GIST) is commonly treated with tyrosine kinase inhibitors (TKIs), but most patients ultimately develop secondary resistance. Cabozantinib, a multi-targeted TKI inhibitor, has activity in patient-derived GIST mouse xenograft models and can overcome compensatory MET signalling occurring on TKI treatment. European Organisation for Treatment of Cancer (EORTC) 1317 &apos;CaboGIST&apos; assessed the safety and activity of cabozantinib in patients with GIST who had progressed on imatinib and sunitinib. Methods: In this multi-center, open label, single arm phase II study, eligible GIST patients received oral cabozantinib (60 mg) once daily. Primary end-point was the progression-free survival rate at 12 weeks assessed by the local investigator per Response Evaluation Criteria in Solid Tumours 1.1. If at least 21 of the first 41 eligible and evaluable patients were progression-free at week 12, the activity of cabozantinib was sufficient to warrant further exploration according to the A&apos;Hern one-stage study design. Findings: A total of 50 eligible patients started treatment between 02/2017 and 08/2018, including four (8%) still continuing cabozantinib at clinical cut-off (09/2019). The number of 3-weekly treatment cycles ranged from 1 to 30. Among the first 41 eligible and evaluable patients, 24 were progression-free at week 12 (58.5%, 95% confidence interval [CI] 42.0-74.0%). Among all 50 patients, 30 were progression-free at week 12 (60%, 95% CI 45-74%). Seven patients achieved a partial response (14%, 95% CI 6-27%), and 34 had stable disease (68%, 95% CI 53-80%) as best response. Progression was seen in eight patients (16%, 95% CI 7-29%), and one was not evaluable. Disease control was achieved in 41 patients (82%, 95% CI 69-91%). Median progression-free survival was 5.5 months (95% CI 3.6-6.9). The most common adverse events were diarrhoea (76%), palmar-plantar erythrodysesthesia syndrome (60%), fatigue (50%), hypertension (42%), weight loss (40%) and oral mucositis (30%), with 32 (64%) patients requiring dose reductions, 27 (54%) having treatment interruptions and no cabozantinib-related deaths observed. Interpretation: EORTC 1317 met its primary end-point, with 24/41 patients being progression-free at week 12 of treatment. The objective response was 14% with an encouraging disease control rate of 82%. Results of this trial confirm preclinical findings and warrant further exploration of cabozantinib in GIST. Clinical trial numbers: EORTC 1317, NCT02216578, EudraCT 2014-000501-13.

  • Název v anglickém jazyce

    Activity and safety of the multi-target tyrosine kinase inhibitor cabozantinib in patients with metastatic gastrointestinal stromal tumour after treatment with imatinib and sunitinib: European Organisation for Research and Treatment of Cancer phase II trial 1317 'CaboGIST'

  • Popis výsledku anglicky

    Background: Gastrointestinal stromal tumour (GIST) is commonly treated with tyrosine kinase inhibitors (TKIs), but most patients ultimately develop secondary resistance. Cabozantinib, a multi-targeted TKI inhibitor, has activity in patient-derived GIST mouse xenograft models and can overcome compensatory MET signalling occurring on TKI treatment. European Organisation for Treatment of Cancer (EORTC) 1317 &apos;CaboGIST&apos; assessed the safety and activity of cabozantinib in patients with GIST who had progressed on imatinib and sunitinib. Methods: In this multi-center, open label, single arm phase II study, eligible GIST patients received oral cabozantinib (60 mg) once daily. Primary end-point was the progression-free survival rate at 12 weeks assessed by the local investigator per Response Evaluation Criteria in Solid Tumours 1.1. If at least 21 of the first 41 eligible and evaluable patients were progression-free at week 12, the activity of cabozantinib was sufficient to warrant further exploration according to the A&apos;Hern one-stage study design. Findings: A total of 50 eligible patients started treatment between 02/2017 and 08/2018, including four (8%) still continuing cabozantinib at clinical cut-off (09/2019). The number of 3-weekly treatment cycles ranged from 1 to 30. Among the first 41 eligible and evaluable patients, 24 were progression-free at week 12 (58.5%, 95% confidence interval [CI] 42.0-74.0%). Among all 50 patients, 30 were progression-free at week 12 (60%, 95% CI 45-74%). Seven patients achieved a partial response (14%, 95% CI 6-27%), and 34 had stable disease (68%, 95% CI 53-80%) as best response. Progression was seen in eight patients (16%, 95% CI 7-29%), and one was not evaluable. Disease control was achieved in 41 patients (82%, 95% CI 69-91%). Median progression-free survival was 5.5 months (95% CI 3.6-6.9). The most common adverse events were diarrhoea (76%), palmar-plantar erythrodysesthesia syndrome (60%), fatigue (50%), hypertension (42%), weight loss (40%) and oral mucositis (30%), with 32 (64%) patients requiring dose reductions, 27 (54%) having treatment interruptions and no cabozantinib-related deaths observed. Interpretation: EORTC 1317 met its primary end-point, with 24/41 patients being progression-free at week 12 of treatment. The objective response was 14% with an encouraging disease control rate of 82%. Results of this trial confirm preclinical findings and warrant further exploration of cabozantinib in GIST. Clinical trial numbers: EORTC 1317, NCT02216578, EudraCT 2014-000501-13.

Klasifikace

  • Druh

    J<sub>imp</sub> - Článek v periodiku v databázi Web of Science

  • CEP obor

  • OECD FORD obor

    30204 - Oncology

Návaznosti výsledku

  • Projekt

  • Návaznosti

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Ostatní

  • Rok uplatnění

    2020

  • Kód důvěrnosti údajů

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Údaje specifické pro druh výsledku

  • Název periodika

    European Journal of Cancer

  • ISSN

    0959-8049

  • e-ISSN

  • Svazek periodika

    134

  • Číslo periodika v rámci svazku

    July

  • Stát vydavatele periodika

    GB - Spojené království Velké Británie a Severního Irska

  • Počet stran výsledku

    13

  • Strana od-do

    62-74

  • Kód UT WoS článku

    000541253400010

  • EID výsledku v databázi Scopus

    2-s2.0-85085351029