Treatment of metastatic ALK-positive non-small cell lung cancer: real-world outcomes in a single center study

被引:0
作者
Kamali, Caroline [1 ,2 ]
Tsakonas, Georgios [1 ,2 ]
Hydbring, Per [1 ]
Jatta, Kenbugul [1 ]
Berglund, Anders [3 ]
Viktorsson, Kristina [1 ]
Lewensohn, Rolf [1 ,2 ]
De Petris, Luigi [1 ,2 ]
Ekman, Simon [1 ,2 ]
机构
[1] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden
[2] Karolinska Univ Hosp, Thorac Oncol Ctr, Med Unit Head & Neck Lung & Skin Canc, Theme Canc, Stockholm, Sweden
[3] EpiStat AB, Uppsala, Sweden
关键词
Advanced non-small cell lung cancer (advanced NSCLC); anaplastic lymphoma kinase (ALK); tyrosine kinase inhibitor (TKI); real-world data; long-term survival outcomes; CRIZOTINIB; LORLATINIB; ALECTINIB; SURVIVAL; EFFICACY; THERAPY; SAFETY;
D O I
10.21037/tlcr-24-396
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Rearrangement in anaplastic lymphoma kinase (ALK) occurs in 4-7% of non-small cell lung cancer (NSCLC) cases. Despite improved survival with tyrosine kinase inhibitors (TKIs), treatment resistance remains challenging. This retrospective study analyzed advanced ALK-positive NSCLC patients, focusing on clinical aspects, treatments, resistance, and outcomes. Methods: Patients diagnosed between January 2009 and December 2021 who received at least one ALKTKI line at the Karolinska University Hospital, were included. We evaluated crizotinib or 2 nd generation ALK-TKI effectiveness in first-line treatment and lorlatinib in subsequent lines. Overall survival (OS) was defined as from the date of advanced lung cancer diagnosis until the date of last follow-up (April 22, 2022) or the date of death from any cause. Progression-free survival (PFS), from the date of starting ALK-TKI until the date of progression, death, or last follow-up. Resistance mechanisms were assessed through re-biopsies utilizing next-generation sequencing (NGS). Results: Out of 160 eligible patients, 10 were excluded. Median follow-up was 54.0 months from diagnosis and 45.0 months from initial ALK-TKI treatment. Crizotinib showed a median PFS of 8.0 months and a median OS of 35.0 months. Second generation ALK-TKIs demonstrated a median PFS of 52.0 months [OS was not reached (NR)]. Overall, the median OS was 65.0 months. Poor prognostic factors included male sex, thromboembolism, crizotinib treatment, and chronic obstructive pulmonary disease (COPD)/asthma. Rebiopsies in 18 cases revealed secondary ALK mutations in 8 patients, correlating with a shorter median PFS in subsequent ALK-TKI treatment (1.0 vs. 7.0 months). Conclusions: This comprehensive study, spanning over a decade, provides crucial insights into the clinical characteristics, treatment patterns, and resistance mechanisms of advanced ALK-positive NSCLC, where median OS exceeds 5 years. Re-biopsies during treatment are essential for advancing our understanding of resistance mechanisms and the tumor dynamics evolving during ALK-TKI therapy.
引用
收藏
页码:2918 / 2933
页数:20
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