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

Autor:	Kamali C; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.; Theme Cancer, Medical Unit Head, and Neck, Lung and Skin Cancer, Thoracic Oncology Center, Karolinska University Hospital, Stockholm, Sweden., Tsakonas G; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.; Theme Cancer, Medical Unit Head, and Neck, Lung and Skin Cancer, Thoracic Oncology Center, Karolinska University Hospital, Stockholm, Sweden., Hydbring P; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Jatta K; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Berglund A; EpiStat AB, Uppsala, Sweden., Viktorsson K; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Lewensohn R; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.; Theme Cancer, Medical Unit Head, and Neck, Lung and Skin Cancer, Thoracic Oncology Center, Karolinska University Hospital, Stockholm, Sweden., De Petris L; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.; Theme Cancer, Medical Unit Head, and Neck, Lung and Skin Cancer, Thoracic Oncology Center, Karolinska University Hospital, Stockholm, Sweden., Ekman S; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.; Theme Cancer, Medical Unit Head, and Neck, Lung and Skin Cancer, Thoracic Oncology Center, Karolinska University Hospital, Stockholm, Sweden.
Jazyk:	angličtina
Zdroj:	Translational lung cancer research [Transl Lung Cancer Res] 2024 Nov 30; Vol. 13 (11), pp. 2918-2933. Date of Electronic Publication: 2024 Nov 12.
DOI:	10.21037/tlcr-24-396
Abstrakt:	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 ALK-TKI 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. Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-396/coif). G.T. reports honoraria from MSD, Roche AB for lectures and reports paid participation at ELCC 2023 from Roche AB. K.V. is supported for salary and other project related costs by the indicated private funding bodies or region grants Stockholm Cancer Society (contract No. 221383), Stockholm County Council (contract Nos. 909121, 750032, and FoUI-966345), and Erling Persson Family Foundation. R.L. reports grant from the Swedish Cancer Society (No. CAN2021/1469), the Stockholm Cancer Society (No. 221212), the Stockholm County Council (contract Nos. FoUI-966345, 909121, and 750032), the Erling Persson Family Foundation, and the Swedish Foundation for Strategic Research (No. SIP21-0106). S.E. reports grants from the Swedish Cancer Society (grant No. CAN2023/2919), the King Gustaf V Jubilee Fund (grant No. 204053), the Sjöberg Foundation (No. 2022-2024), and the Stockholm County Council (No. 987911). The other authors have no conflicts of interest to declare. (2024 AME Publishing Company. All rights reserved.)
Databáze:	MEDLINE
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