Lung cancer is the leading cause of cancer-related deaths globally. A trial for a new anti-cancer drug showed that five years post-treatment, 60% of patients with a common form of lung cancer were still alive, with their cancer not progressing. This trial targeted the ALK protein, which is produced by the ALK gene. In non-small cell lung cancer (NSCLC), this gene can be rearranged, leading to aggressive cancer growth. ALK-positive tumors occur in about 3% to 5% of NSCLC cases, usually affecting younger, light, or non-smokers.
Lorlatinib, a third-generation ALK inhibitor, was tested in an international clinical trial led by Peter MacCallum Cancer Center in Melbourne, Australia. The study focused on patients with advanced ALK-positive NSCLC. In this Phase III trial, 296 patients were randomly assigned to receive either lorlatinib or crizotinib, a first-generation ALK inhibitor. The primary endpoint was progression-free survival, with secondary endpoints including overall survival and brain metastasis.
Results revealed that 60% of patients on lorlatinib were alive without disease progression five years after treatment, compared to 8% on crizotinib. Lorlatinib showed an 81% reduction in cancer progression or death and a 94% reduction in brain metastasis progression compared to crizotinib. The updated analysis confirmed that lorlatinib helps patients live longer without disease progression, with many patients experiencing sustained benefits for over five years.
Despite higher adverse event rates with lorlatinib compared to crizotinib (77% versus 57%), these events were manageable with dose adjustments and did not affect the drug’s efficacy. The study, presenting the longest progression-free survival data for any single-agent targeted treatment in advanced NSCLC, marks significant progress in lung cancer treatment. The trial results were highlighted at the 2024 American Society of Clinical Oncology (ASCO) meeting and published in the Journal of Clinical Oncology.
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