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

Caroline Kamali; Georgios Tsakonas; Per Hydbring; Kenbugul Jatta; Anders Berglund; Kristina Viktorsson; Rolf Lewensohn; Luigi De Petris; Simon Ekman

doi:10.21037/tlcr-24-396

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

Transl Lung Cancer Res. 2024 Nov 30;13(11):2918-2933. doi: 10.21037/tlcr-24-396. Epub 2024 Nov 12.

Authors

Caroline Kamali^{1

2}, Georgios Tsakonas^{1

2}, Per Hydbring¹, Kenbugul Jatta¹, Anders Berglund³, Kristina Viktorsson¹, Rolf Lewensohn^{1

2}, Luigi De Petris^{1

2}, Simon Ekman^{1

2}

Affiliations

¹ Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
² Theme Cancer, Medical Unit Head, and Neck, Lung and Skin Cancer, Thoracic Oncology Center, Karolinska University Hospital, Stockholm, Sweden.
³ EpiStat AB, Uppsala, Sweden.

Abstract

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.

Keywords: Advanced non-small cell lung cancer (advanced NSCLC); anaplastic lymphoma kinase (ALK); long-term survival outcomes; real-world data; tyrosine kinase inhibitor (TKI).