Onkológia 4/2024

Lorlatinib in 1st line ALK-positive non-small cell lung cancer

Lung cancer is one of the most common cancers worldwide and is associated with high mortality. In men, mortality has a clear priority, which is up to 21.5% of all tumors, and in women, it earned the second place, right after breast cancer, which is 13.7% (Globocan2020). About 60% of all lung tumors belong to the group of non-small cell histological subtype. ALK (anaplastic lymphoma kinase) is a confirmed tyrosine kinase target in several tumors, including non-small cell lung cancer. Among the first successful molecules in the treatment of metastatic non-small cell carcinoma of ALK+ patients was the 1st generation ALK inhibitor - crizotinib. In an effort to overcome resistance to crizotinib, the development of new drugs has advanced significantly. Based on the ALEX, ALTA-1L and CROWN clinical studies, the second-generation ALK inhibitors alectinib and brigatinib and the third-generation lorlatinib uncompromisingly displaced crizotinib from the first-line regimen due to much higher systemic efficacy and a significantly better effect in the CNS. Lorlatinib improved progression-free survival (PFS) and intracranial activity compared with crizotinib in patients with previously untreated, advanced, ALK-positive non-small cell lung cancer in the phase III CROWN trial. Currently, in May 2024, the results of the 5-year analysis of the CROWN clinical trial were published at the ASCO conference (American Society of Clinical Oncology) in Chicago.

Keywords: metastatic non-small cell lung cancer, EML4-ALK rearrangement, lorlatinib, intracranial efficacy, CROWN, brain metastases