Efficacy and Clinical Outcomes of Crizotinib in Patients with ROS1-Rearranged NSCLC: A Multicenter Study

<i>Background and Objectives:</i> ROS1 rearrangement is a rare but targetable alteration in non-small-cell lung cancer (NSCLC), occurring in 1–2% of cases. Crizotinib, a tyrosine kinase inhibitor, has demonstrated efficacy in clinical trials, but real-world data remain limited. This stud...

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Main Authors: Alper Topal, Goncagul Akdag, Sedat Yildirim, Oguzcan Kinikoglu, Deniz Isik, Gizem Yildirim, Salih Tunbekici, Fatih Kus, Aydın Acarbay, Murad Guliyev, Nargiz Majidova, Yasin Kutlu, Mustafa Erman, Hatice Odabas, Nedim Turan, Nuri Karadurmus
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Medicina
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Online Access:https://www.mdpi.com/1648-9144/61/3/490
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author Alper Topal
Goncagul Akdag
Sedat Yildirim
Oguzcan Kinikoglu
Deniz Isik
Gizem Yildirim
Salih Tunbekici
Fatih Kus
Aydın Acarbay
Murad Guliyev
Nargiz Majidova
Yasin Kutlu
Mustafa Erman
Hatice Odabas
Nedim Turan
Nuri Karadurmus
author_facet Alper Topal
Goncagul Akdag
Sedat Yildirim
Oguzcan Kinikoglu
Deniz Isik
Gizem Yildirim
Salih Tunbekici
Fatih Kus
Aydın Acarbay
Murad Guliyev
Nargiz Majidova
Yasin Kutlu
Mustafa Erman
Hatice Odabas
Nedim Turan
Nuri Karadurmus
author_sort Alper Topal
collection DOAJ
description <i>Background and Objectives:</i> ROS1 rearrangement is a rare but targetable alteration in non-small-cell lung cancer (NSCLC), occurring in 1–2% of cases. Crizotinib, a tyrosine kinase inhibitor, has demonstrated efficacy in clinical trials, but real-world data remain limited. This study evaluates the safety and efficacy of crizotinib in ROS1-rearranged NSCLC patients in a real-world setting. <i>Materials and Methods:</i> This multicenter, retrospective research included 43 individuals with advanced/metastatic NSCLC and confirmed ROS1 rearrangements. Patients were treated with crizotinib in first- or second-line settings. Efficacy endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Safety was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. <i>Results:</i> The median follow-up was 45.8 months. The ORR for first-line crizotinib was 72.1%, with a DCR of 79%. The median PFS was 20.9 months (95% CI: 6.02–35.69), and the median OS was 52.7 months (95% CI: 13.08–92.31). ECOG performance status was a significant prognostic factor for ORR (<i>p</i> = 0.02). The most common adverse events were fatigue (16.2%), elevated transaminases (13.9%), and vision disorders (11.6%). All reported adverse events were grade 1 or 2, with no grade ≥ 3 events observed. <i>Conclusions:</i>Crizotinib demonstrated significant efficacy and a favorable safety profile in real-world individuals with ROS1-rearranged NSCLC. These findings align with pivotal trials, underscoring crizotinib’s role as a standard treatment for this molecular subset. Further prospective studies are warranted to explore intracranial efficacy and long-term outcomes.
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spelling doaj-art-b43b14acd3404ea29fba10ebc5c5f9b82025-08-20T02:42:22ZengMDPI AGMedicina1010-660X1648-91442025-03-0161349010.3390/medicina61030490Efficacy and Clinical Outcomes of Crizotinib in Patients with ROS1-Rearranged NSCLC: A Multicenter StudyAlper Topal0Goncagul Akdag1Sedat Yildirim2Oguzcan Kinikoglu3Deniz Isik4Gizem Yildirim5Salih Tunbekici6Fatih Kus7Aydın Acarbay8Murad Guliyev9Nargiz Majidova10Yasin Kutlu11Mustafa Erman12Hatice Odabas13Nedim Turan14Nuri Karadurmus15Department of Medical Oncology, Health Science University, Gulhane Research and Training Hospital, Ankara 06010, TurkeyDepartment of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Istanbul 34865, TurkeyDepartment of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Istanbul 34865, TurkeyDepartment of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Istanbul 34865, TurkeyDepartment of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Istanbul 34865, TurkeyDepartment of Medical Oncology, Health Science University, Gulhane Research and Training Hospital, Ankara 06010, TurkeyDivision of Medical Oncology, Departmant of Internal Medicine, Ege Universitiy, Izmir 35100, TurkeyDepartment of Medical Oncology, Hacettepe University Oncology Institue, Ankara 06230, TurkeyDivision of Medical Oncology, Departmant of Internal Medicine, Istanbul Medeniyet University, Istanbul 34730, TurkeyDivision of Medical Oncology, Departmant of Internal Medicine, Istanbul University-Cerrahpasa, Istanbul 34098, TurkeyDepartment of Medical Oncology, Marmara University Pendik Training and Research Hospital, Istanbul 34854, TurkeyDepartment of Medical Oncology, Tokat State Hospital, Tokat 60000, TurkeyDepartment of Medical Oncology, Hacettepe University Oncology Institue, Ankara 06230, TurkeyDepartment of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Istanbul 34865, TurkeyDepartment of Medical Oncology, Kartal Dr. Lütfi Kirdar City Hospital, Health Science University, Istanbul 34865, TurkeyDepartment of Medical Oncology, Health Science University, Gulhane Research and Training Hospital, Ankara 06010, Turkey<i>Background and Objectives:</i> ROS1 rearrangement is a rare but targetable alteration in non-small-cell lung cancer (NSCLC), occurring in 1–2% of cases. Crizotinib, a tyrosine kinase inhibitor, has demonstrated efficacy in clinical trials, but real-world data remain limited. This study evaluates the safety and efficacy of crizotinib in ROS1-rearranged NSCLC patients in a real-world setting. <i>Materials and Methods:</i> This multicenter, retrospective research included 43 individuals with advanced/metastatic NSCLC and confirmed ROS1 rearrangements. Patients were treated with crizotinib in first- or second-line settings. Efficacy endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Safety was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. <i>Results:</i> The median follow-up was 45.8 months. The ORR for first-line crizotinib was 72.1%, with a DCR of 79%. The median PFS was 20.9 months (95% CI: 6.02–35.69), and the median OS was 52.7 months (95% CI: 13.08–92.31). ECOG performance status was a significant prognostic factor for ORR (<i>p</i> = 0.02). The most common adverse events were fatigue (16.2%), elevated transaminases (13.9%), and vision disorders (11.6%). All reported adverse events were grade 1 or 2, with no grade ≥ 3 events observed. <i>Conclusions:</i>Crizotinib demonstrated significant efficacy and a favorable safety profile in real-world individuals with ROS1-rearranged NSCLC. These findings align with pivotal trials, underscoring crizotinib’s role as a standard treatment for this molecular subset. Further prospective studies are warranted to explore intracranial efficacy and long-term outcomes.https://www.mdpi.com/1648-9144/61/3/490ROS1lung cancercrizotinib
spellingShingle Alper Topal
Goncagul Akdag
Sedat Yildirim
Oguzcan Kinikoglu
Deniz Isik
Gizem Yildirim
Salih Tunbekici
Fatih Kus
Aydın Acarbay
Murad Guliyev
Nargiz Majidova
Yasin Kutlu
Mustafa Erman
Hatice Odabas
Nedim Turan
Nuri Karadurmus
Efficacy and Clinical Outcomes of Crizotinib in Patients with ROS1-Rearranged NSCLC: A Multicenter Study
Medicina
ROS1
lung cancer
crizotinib
title Efficacy and Clinical Outcomes of Crizotinib in Patients with ROS1-Rearranged NSCLC: A Multicenter Study
title_full Efficacy and Clinical Outcomes of Crizotinib in Patients with ROS1-Rearranged NSCLC: A Multicenter Study
title_fullStr Efficacy and Clinical Outcomes of Crizotinib in Patients with ROS1-Rearranged NSCLC: A Multicenter Study
title_full_unstemmed Efficacy and Clinical Outcomes of Crizotinib in Patients with ROS1-Rearranged NSCLC: A Multicenter Study
title_short Efficacy and Clinical Outcomes of Crizotinib in Patients with ROS1-Rearranged NSCLC: A Multicenter Study
title_sort efficacy and clinical outcomes of crizotinib in patients with ros1 rearranged nsclc a multicenter study
topic ROS1
lung cancer
crizotinib
url https://www.mdpi.com/1648-9144/61/3/490
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