Real-World Outcomes of Crizotinib in ROS1-Rearranged Advanced Non-Small-Cell Lung Cancer
Real-world data on the use and outcomes of crizotinib in ROS1-rearranged non-small-cell lung cancer (NSCLC) are limited. This study aims to analyze the real-world efficacy of crizotinib in South Korea and explore the utilization of liquid biopsies that implement next-generation sequencing (NGS) usin...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-01-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/16/3/528 |
| _version_ | 1797319019317952512 |
|---|---|
| author | Hyeon Hwa Kim Jae Cheol Lee In-Jae Oh Eun Young Kim Seong Hoon Yoon Shin Yup Lee Min Ki Lee Jeong Eun Lee Chan Kwon Park Kye Young Lee Sung Yong Lee Seung Joon Kim Jun Hyeok Lim Chang-min Choi |
| author_facet | Hyeon Hwa Kim Jae Cheol Lee In-Jae Oh Eun Young Kim Seong Hoon Yoon Shin Yup Lee Min Ki Lee Jeong Eun Lee Chan Kwon Park Kye Young Lee Sung Yong Lee Seung Joon Kim Jun Hyeok Lim Chang-min Choi |
| author_sort | Hyeon Hwa Kim |
| collection | DOAJ |
| description | Real-world data on the use and outcomes of crizotinib in ROS1-rearranged non-small-cell lung cancer (NSCLC) are limited. This study aims to analyze the real-world efficacy of crizotinib in South Korea and explore the utilization of liquid biopsies that implement next-generation sequencing (NGS) using cell-free total nucleic acids. In this prospective multicenter cohort study, 40 patients with ROS1-rearranged NSCLC, either starting or already on crizotinib, were enrolled. Patients had a median age of 61 years, with 32.5% presenting brain/central nervous system (CNS) metastases at treatment initiation. At the data cutoff, 48.0% were still in treatment; four continued with it even after disease progression due to the clinical benefits. The objective response rate was 70.0%, with a median duration of response of 27.8 months. The median progression-free survival was 24.1 months, while the median overall survival was not reached. Adverse events occurred in 90.0% of patients, primarily with elevated transaminases, yet these were mostly manageable. The NGS assay detected a CD74–ROS1 fusion in 2 of the 14 patients at treatment initiation and identified emerging mutations, such as ROS1 G2032R, ROS1 D2033N, and KRAS G12D, during disease progression. These findings confirm crizotinib’s sustained clinical efficacy and safety in a real-world context, which was characterized by a higher elderly population and higher rates of brain/CNS metastases. The study highlights the clinical relevance of liquid biopsy for detecting resistance mechanisms, suggesting its value in personalized treatment strategies. |
| first_indexed | 2024-03-08T03:59:51Z |
| format | Article |
| id | doaj.art-a3521226bba34c7b8ad9934d24766038 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-08T03:59:51Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a3521226bba34c7b8ad9934d247660382024-02-09T15:08:53ZengMDPI AGCancers2072-66942024-01-0116352810.3390/cancers16030528Real-World Outcomes of Crizotinib in ROS1-Rearranged Advanced Non-Small-Cell Lung CancerHyeon Hwa Kim0Jae Cheol Lee1In-Jae Oh2Eun Young Kim3Seong Hoon Yoon4Shin Yup Lee5Min Ki Lee6Jeong Eun Lee7Chan Kwon Park8Kye Young Lee9Sung Yong Lee10Seung Joon Kim11Jun Hyeok Lim12Chang-min Choi13Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of KoreaDepartment of Oncology, Asan Medical Centre, University of Ulsan College of Medicine, Seoul 05505, Republic of KoreaDepartment of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Gwangju 58128, Republic of KoreaDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaDepartment of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of KoreaDepartment of Internal Medicine, Kyungpook National University School of Medicine, Daegu 41404, Republic of KoreaDivision of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Pusan National University Hospital, Busan 49241, Republic of KoreaDivision of Pulmonology, Department of Internal Medicine, Chungnam National University, Daejeon 34134, Republic of KoreaDivision of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 16247, Republic of KoreaDepartments of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul 05030, Republic of KoreaDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul 08308, Republic of KoreaDivision of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul 16247, Republic of KoreaDepartment of Internal Medicine, Inha University Hospital, Incheon 22332, Republic of KoreaDivision of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of KoreaReal-world data on the use and outcomes of crizotinib in ROS1-rearranged non-small-cell lung cancer (NSCLC) are limited. This study aims to analyze the real-world efficacy of crizotinib in South Korea and explore the utilization of liquid biopsies that implement next-generation sequencing (NGS) using cell-free total nucleic acids. In this prospective multicenter cohort study, 40 patients with ROS1-rearranged NSCLC, either starting or already on crizotinib, were enrolled. Patients had a median age of 61 years, with 32.5% presenting brain/central nervous system (CNS) metastases at treatment initiation. At the data cutoff, 48.0% were still in treatment; four continued with it even after disease progression due to the clinical benefits. The objective response rate was 70.0%, with a median duration of response of 27.8 months. The median progression-free survival was 24.1 months, while the median overall survival was not reached. Adverse events occurred in 90.0% of patients, primarily with elevated transaminases, yet these were mostly manageable. The NGS assay detected a CD74–ROS1 fusion in 2 of the 14 patients at treatment initiation and identified emerging mutations, such as ROS1 G2032R, ROS1 D2033N, and KRAS G12D, during disease progression. These findings confirm crizotinib’s sustained clinical efficacy and safety in a real-world context, which was characterized by a higher elderly population and higher rates of brain/CNS metastases. The study highlights the clinical relevance of liquid biopsy for detecting resistance mechanisms, suggesting its value in personalized treatment strategies.https://www.mdpi.com/2072-6694/16/3/528ROS1non-small-cell lung cancercrizotinibreal-world efficacy |
| spellingShingle | Hyeon Hwa Kim Jae Cheol Lee In-Jae Oh Eun Young Kim Seong Hoon Yoon Shin Yup Lee Min Ki Lee Jeong Eun Lee Chan Kwon Park Kye Young Lee Sung Yong Lee Seung Joon Kim Jun Hyeok Lim Chang-min Choi Real-World Outcomes of Crizotinib in ROS1-Rearranged Advanced Non-Small-Cell Lung Cancer Cancers ROS1 non-small-cell lung cancer crizotinib real-world efficacy |
| title | Real-World Outcomes of Crizotinib in ROS1-Rearranged Advanced Non-Small-Cell Lung Cancer |
| title_full | Real-World Outcomes of Crizotinib in ROS1-Rearranged Advanced Non-Small-Cell Lung Cancer |
| title_fullStr | Real-World Outcomes of Crizotinib in ROS1-Rearranged Advanced Non-Small-Cell Lung Cancer |
| title_full_unstemmed | Real-World Outcomes of Crizotinib in ROS1-Rearranged Advanced Non-Small-Cell Lung Cancer |
| title_short | Real-World Outcomes of Crizotinib in ROS1-Rearranged Advanced Non-Small-Cell Lung Cancer |
| title_sort | real world outcomes of crizotinib in ros1 rearranged advanced non small cell lung cancer |
| topic | ROS1 non-small-cell lung cancer crizotinib real-world efficacy |
| url | https://www.mdpi.com/2072-6694/16/3/528 |
| work_keys_str_mv | AT hyeonhwakim realworldoutcomesofcrizotinibinros1rearrangedadvancednonsmallcelllungcancer AT jaecheollee realworldoutcomesofcrizotinibinros1rearrangedadvancednonsmallcelllungcancer AT injaeoh realworldoutcomesofcrizotinibinros1rearrangedadvancednonsmallcelllungcancer AT eunyoungkim realworldoutcomesofcrizotinibinros1rearrangedadvancednonsmallcelllungcancer AT seonghoonyoon realworldoutcomesofcrizotinibinros1rearrangedadvancednonsmallcelllungcancer AT shinyuplee realworldoutcomesofcrizotinibinros1rearrangedadvancednonsmallcelllungcancer AT minkilee realworldoutcomesofcrizotinibinros1rearrangedadvancednonsmallcelllungcancer AT jeongeunlee realworldoutcomesofcrizotinibinros1rearrangedadvancednonsmallcelllungcancer AT chankwonpark realworldoutcomesofcrizotinibinros1rearrangedadvancednonsmallcelllungcancer AT kyeyounglee realworldoutcomesofcrizotinibinros1rearrangedadvancednonsmallcelllungcancer AT sungyonglee realworldoutcomesofcrizotinibinros1rearrangedadvancednonsmallcelllungcancer AT seungjoonkim realworldoutcomesofcrizotinibinros1rearrangedadvancednonsmallcelllungcancer AT junhyeoklim realworldoutcomesofcrizotinibinros1rearrangedadvancednonsmallcelllungcancer AT changminchoi realworldoutcomesofcrizotinibinros1rearrangedadvancednonsmallcelllungcancer |