Cited 8 times in
Early Circulating Tumor DNA Dynamics and Efficacy of Lorlatinib in Patients With Treatment-Naive, Advanced, ALK-Positive NSCLC
DC Field | Value | Language |
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dc.contributor.author | 김혜련 | - |
dc.date.accessioned | 2024-03-22T05:53:07Z | - |
dc.date.available | 2024-03-22T05:53:07Z | - |
dc.date.issued | 2023-11 | - |
dc.identifier.issn | 1556-0864 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/198269 | - |
dc.description.abstract | Introduction: Circulating tumor DNA (ctDNA) has been used as a biomarker for prognostication and response to treatment. Here, we evaluate ctDNA as a potential biomarker for response to lorlatinib, a third-generation ALK tyrosine kinase inhibitor in patients with treatment-naive, advanced, ALK-positive NSCLC in the ongoing phase 3 CROWN study (NCT03052608).Methods: Molecular responses were calculated using mean variant allele frequency (VAF), longitudinal mean change in VAF (dVAF), and ratio to baseline. Efficacy assessments (progression-free survival [PFS] and objective response rate) were paired with individual patient ctDNA and analyzed for association.Results: Compared with baseline, mean VAF at week 4 was decreased in both treatment arms. Considering all detected somatic variants, a reduction in dVAF (<= 0) was associated with a longer PFS in the lorlatinib arm. The hazard ratio (HR) for a dVAF less than or equal to 0 versus more than 0 was 0.50 (95% confidence interval [CI]: 0.23-1.12) in the lorlatinib arm. A similar association was not observed for crizotinib (HR = 1.00, 95% CI: 0.49-2.03). Comparing molecular responders with nonresponders, patients treated with lorlatinib who had a molecular response had longer PFS (HR = 0.37, 95% CI: 0.16-0.85); patients treated with crizotinib who had a molecular response had similar PFS as those without a molecular response (HR = 1.48, 95% CI: 0.67-3.30).Conclusions: In patients with treatment-naive, advanced, ALK-positive NSCLC, early ctDNA dynamics predicted better outcome with lorlatinib but not with crizotinib. These results suggest that ctDNA may be used to monitor and potentially predict efficacy of lorlatinib treatment.(c) 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Elsevier | - |
dc.relation.isPartOf | JOURNAL OF THORACIC ONCOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Anaplastic Lymphoma Kinase / genetics | - |
dc.subject.MESH | Biomarkers | - |
dc.subject.MESH | Carcinoma, Non-Small-Cell Lung* / genetics | - |
dc.subject.MESH | Circulating Tumor DNA* | - |
dc.subject.MESH | Crizotinib | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Lactams, Macrocyclic / therapeutic use | - |
dc.subject.MESH | Lung Neoplasms* / drug therapy | - |
dc.subject.MESH | Lung Neoplasms* / genetics | - |
dc.subject.MESH | Protein Kinase Inhibitors / adverse effects | - |
dc.title | Early Circulating Tumor DNA Dynamics and Efficacy of Lorlatinib in Patients With Treatment-Naive, Advanced, ALK-Positive NSCLC | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Ross A Soo | - |
dc.contributor.googleauthor | Jean-François Martini | - |
dc.contributor.googleauthor | Anthonie J van der Wekken | - |
dc.contributor.googleauthor | Shunsuke Teraoka | - |
dc.contributor.googleauthor | Roberto Ferrara | - |
dc.contributor.googleauthor | Alice T Shaw | - |
dc.contributor.googleauthor | Deborah Shepard | - |
dc.contributor.googleauthor | Anna Maria Calella | - |
dc.contributor.googleauthor | Anna Polli | - |
dc.contributor.googleauthor | Francesca Toffalorio | - |
dc.contributor.googleauthor | Pascale Tomasini | - |
dc.contributor.googleauthor | Chao-Hua Chiu | - |
dc.contributor.googleauthor | Dariusz M Kowalski | - |
dc.contributor.googleauthor | Hye Ryun Kim | - |
dc.contributor.googleauthor | Benjamin J Solomon | - |
dc.identifier.doi | 10.1016/j.jtho.2023.05.021 | - |
dc.contributor.localId | A01166 | - |
dc.relation.journalcode | J01909 | - |
dc.identifier.eissn | 1556-1380 | - |
dc.identifier.pmid | 37295609 | - |
dc.subject.keyword | ALK | - |
dc.subject.keyword | Circulating tumor DNA | - |
dc.subject.keyword | Lorlatinib | - |
dc.subject.keyword | Non–small cell lung cancer | - |
dc.subject.keyword | Tyrosine kinase inhibitor | - |
dc.contributor.alternativeName | Kim, Hye Ryun | - |
dc.contributor.affiliatedAuthor | 김혜련 | - |
dc.citation.volume | 18 | - |
dc.citation.number | 11 | - |
dc.citation.startPage | 1568 | - |
dc.citation.endPage | 1580 | - |
dc.identifier.bibliographicCitation | JOURNAL OF THORACIC ONCOLOGY, Vol.18(11) : 1568-1580, 2023-11 | - |
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