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Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: A real-life data of Turkish Oncology Group

Crizotinib is a multikinase inhibitor, effective in non-small cell lung cancer (NSCLC) harboring mesenchymal-epidermal transition (MET) alterations. Although small prospective studies showed efficacy and safety of crizotinib in NSCLC with MET alterations, there is limited real-life data. Aim of this...

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Autores principales: Gürbüz, Mustafa, Kiliçkap, Saadettin, Bilici, Ahmet, Karadurmuş, Nuri, Sezer, Ahmet, Şendur, Mehmet Ali Nahit, Paydaş, Semra, Artaç, Mehmet, Fulden Yumuk, Perran, Gürsoy, Pinar, Uysal, Mükremin, Şenol Coşkun, Hasan, Tatli, Ali Murat, Selçukbiricik, Fatih, Dişel, Umut, Köksoy, Elif Berna, Güven, Deniz Can, Uğrakli, Muzaffer, Akkuş, Erman, Yücel, Şebnem, Erol, Cihan, Karakaya, Serdar, Şakalar, Teoman, Khanmammadov, Nijat, Paksoy, Nail, Demirkazik, Ahmet
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9771320/
https://www.ncbi.nlm.nih.gov/pubmed/36550824
http://dx.doi.org/10.1097/MD.0000000000032368
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author Gürbüz, Mustafa
Kiliçkap, Saadettin
Bilici, Ahmet
Karadurmuş, Nuri
Sezer, Ahmet
Şendur, Mehmet Ali Nahit
Paydaş, Semra
Artaç, Mehmet
Fulden Yumuk, Perran
Gürsoy, Pinar
Uysal, Mükremin
Şenol Coşkun, Hasan
Tatli, Ali Murat
Selçukbiricik, Fatih
Dişel, Umut
Köksoy, Elif Berna
Güven, Deniz Can
Uğrakli, Muzaffer
Akkuş, Erman
Yücel, Şebnem
Erol, Cihan
Karakaya, Serdar
Şakalar, Teoman
Khanmammadov, Nijat
Paksoy, Nail
Demirkazik, Ahmet
author_facet Gürbüz, Mustafa
Kiliçkap, Saadettin
Bilici, Ahmet
Karadurmuş, Nuri
Sezer, Ahmet
Şendur, Mehmet Ali Nahit
Paydaş, Semra
Artaç, Mehmet
Fulden Yumuk, Perran
Gürsoy, Pinar
Uysal, Mükremin
Şenol Coşkun, Hasan
Tatli, Ali Murat
Selçukbiricik, Fatih
Dişel, Umut
Köksoy, Elif Berna
Güven, Deniz Can
Uğrakli, Muzaffer
Akkuş, Erman
Yücel, Şebnem
Erol, Cihan
Karakaya, Serdar
Şakalar, Teoman
Khanmammadov, Nijat
Paksoy, Nail
Demirkazik, Ahmet
author_sort Gürbüz, Mustafa
collection PubMed
description Crizotinib is a multikinase inhibitor, effective in non-small cell lung cancer (NSCLC) harboring mesenchymal-epidermal transition (MET) alterations. Although small prospective studies showed efficacy and safety of crizotinib in NSCLC with MET alterations, there is limited real-life data. Aim of this study is to investigate real-life efficacy and safety of crizotinib in patients with advanced NSCLC harboring MET alterations. This was a retrospective, multicenter (17 centers) study of Turkish Oncology Group. Patients’ demographic, histological data, treatment, response rates, survival outcomes, and toxicity data were collected. Outcomes were presented for the study population and compared between MET alteration types. Total of 62 patients were included with a median age of 58.5 (range, 26–78). Major histological type was adenocarcinoma, and 3 patients (4.8%) had sarcomatoid component. The most common MET analyzing method was next generation sequencing (90.3%). MET amplification and mutation frequencies were 53.2% (n = 33) and 46.8% (n = 29), respectively. Overall response rate and disease control rate were 56.5% and 74.2% in whole study population, respectively. Median progression free survival (PFS) was 7.2 months (95% confidence interval [CI]: 3.8–10.5), and median overall survival (OS) was 18.7 months (95% CI: 13.7–23.7), regardless of treatment line. Median PFS was 6.1 months (95% CI: 5.6–6.4) for patients with MET amplification, whereas 14.3 months (95% CI: 6.7–21.7) for patients with MET mutation (P = .217). Median PFS was significantly longer in patients who have never smoked (P = .040), have good performance score (P < .001), and responded to the treatment (P < .001). OS was significantly longer in patients with MET mutation (25.6 months, 95% CI: 15.9–35.3) compared to the patients with MET amplification (11.0 months; 95% CI: 5.2–16.8) (P = .049). In never-smokers, median OS was longer than smoker patients (25.6 months [95% CI: 11.8–39.3] vs 16.5 months [95% CI: 9.3–23.6]; P = .049). The most common adverse effects were fatigue (50%), peripheral edema (21%), nausea (29%) and diarrhea (19.4%). Grade 3 or 4 adverse effects were observed in 6.5% of the patients. This real-life data confirms efficacy and safety of crizotinib in the treatment of advanced NSCLC harboring MET alteration.
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spelling pubmed-97713202022-12-23 Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: A real-life data of Turkish Oncology Group Gürbüz, Mustafa Kiliçkap, Saadettin Bilici, Ahmet Karadurmuş, Nuri Sezer, Ahmet Şendur, Mehmet Ali Nahit Paydaş, Semra Artaç, Mehmet Fulden Yumuk, Perran Gürsoy, Pinar Uysal, Mükremin Şenol Coşkun, Hasan Tatli, Ali Murat Selçukbiricik, Fatih Dişel, Umut Köksoy, Elif Berna Güven, Deniz Can Uğrakli, Muzaffer Akkuş, Erman Yücel, Şebnem Erol, Cihan Karakaya, Serdar Şakalar, Teoman Khanmammadov, Nijat Paksoy, Nail Demirkazik, Ahmet Medicine (Baltimore) 5700 Crizotinib is a multikinase inhibitor, effective in non-small cell lung cancer (NSCLC) harboring mesenchymal-epidermal transition (MET) alterations. Although small prospective studies showed efficacy and safety of crizotinib in NSCLC with MET alterations, there is limited real-life data. Aim of this study is to investigate real-life efficacy and safety of crizotinib in patients with advanced NSCLC harboring MET alterations. This was a retrospective, multicenter (17 centers) study of Turkish Oncology Group. Patients’ demographic, histological data, treatment, response rates, survival outcomes, and toxicity data were collected. Outcomes were presented for the study population and compared between MET alteration types. Total of 62 patients were included with a median age of 58.5 (range, 26–78). Major histological type was adenocarcinoma, and 3 patients (4.8%) had sarcomatoid component. The most common MET analyzing method was next generation sequencing (90.3%). MET amplification and mutation frequencies were 53.2% (n = 33) and 46.8% (n = 29), respectively. Overall response rate and disease control rate were 56.5% and 74.2% in whole study population, respectively. Median progression free survival (PFS) was 7.2 months (95% confidence interval [CI]: 3.8–10.5), and median overall survival (OS) was 18.7 months (95% CI: 13.7–23.7), regardless of treatment line. Median PFS was 6.1 months (95% CI: 5.6–6.4) for patients with MET amplification, whereas 14.3 months (95% CI: 6.7–21.7) for patients with MET mutation (P = .217). Median PFS was significantly longer in patients who have never smoked (P = .040), have good performance score (P < .001), and responded to the treatment (P < .001). OS was significantly longer in patients with MET mutation (25.6 months, 95% CI: 15.9–35.3) compared to the patients with MET amplification (11.0 months; 95% CI: 5.2–16.8) (P = .049). In never-smokers, median OS was longer than smoker patients (25.6 months [95% CI: 11.8–39.3] vs 16.5 months [95% CI: 9.3–23.6]; P = .049). The most common adverse effects were fatigue (50%), peripheral edema (21%), nausea (29%) and diarrhea (19.4%). Grade 3 or 4 adverse effects were observed in 6.5% of the patients. This real-life data confirms efficacy and safety of crizotinib in the treatment of advanced NSCLC harboring MET alteration. Lippincott Williams & Wilkins 2022-12-16 /pmc/articles/PMC9771320/ /pubmed/36550824 http://dx.doi.org/10.1097/MD.0000000000032368 Text en Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC) (https://creativecommons.org/licenses/by-nc/4.0/) , where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.
spellingShingle 5700
Gürbüz, Mustafa
Kiliçkap, Saadettin
Bilici, Ahmet
Karadurmuş, Nuri
Sezer, Ahmet
Şendur, Mehmet Ali Nahit
Paydaş, Semra
Artaç, Mehmet
Fulden Yumuk, Perran
Gürsoy, Pinar
Uysal, Mükremin
Şenol Coşkun, Hasan
Tatli, Ali Murat
Selçukbiricik, Fatih
Dişel, Umut
Köksoy, Elif Berna
Güven, Deniz Can
Uğrakli, Muzaffer
Akkuş, Erman
Yücel, Şebnem
Erol, Cihan
Karakaya, Serdar
Şakalar, Teoman
Khanmammadov, Nijat
Paksoy, Nail
Demirkazik, Ahmet
Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: A real-life data of Turkish Oncology Group
title Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: A real-life data of Turkish Oncology Group
title_full Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: A real-life data of Turkish Oncology Group
title_fullStr Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: A real-life data of Turkish Oncology Group
title_full_unstemmed Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: A real-life data of Turkish Oncology Group
title_short Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: A real-life data of Turkish Oncology Group
title_sort crizotinib efficacy and safety in patients with advanced nsclc harboring met alterations: a real-life data of turkish oncology group
topic 5700
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9771320/
https://www.ncbi.nlm.nih.gov/pubmed/36550824
http://dx.doi.org/10.1097/MD.0000000000032368
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