Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma
Ping Yang, Kimary Kulig, Jennifer M Boland, Michele R Erickson-Johnson, Andre M Oliveira, Jason Wampfler, Aminah Jatoi, Claude Deschamps, Randolph Marks, Connie Fortner, Shawn Stoddard, Francis Nichols, Julian Molina, Marie-Christine Aubry, Hui Tang, Eunhee S Yi, Ping Yang, Kimary Kulig, Jennifer M Boland, Michele R Erickson-Johnson, Andre M Oliveira, Jason Wampfler, Aminah Jatoi, Claude Deschamps, Randolph Marks, Connie Fortner, Shawn Stoddard, Francis Nichols, Julian Molina, Marie-Christine Aubry, Hui Tang, Eunhee S Yi
Abstract
Introduction: The EML4-anaplastic lymphoma kinase (ALK) translocation is a recognized oncogenic driver in non-small cell lung cancer. We investigated immunohistochemistry (IHC) screening with fluorescence in situ hybridization (FISH) confirmation for ALK detection and estimated the prevalence of ALK positivity in our patient cohort of never-smokers, together with differences in clinical outcomes and prognostic factors for patients with ALK-positive and ALK-negative tumors.
Methods: We designed a three-phase study (training, validation, and testing) in 300 never-smokers with lung adenocarcinoma from the observational Mayo Clinic Lung Cancer Cohort. Tumor samples were tested using IHC and FISH, and concordance between the methods was assessed. Clinical outcomes were assessed via 5-year progression- or recurrence-free survival from diagnosis. Prognostic factors for ALK-positive tumors and metastases were also investigated.
Results: ALK-positive patients were significantly (p < 0.05) younger and had higher grade tumors than ALK-negative patients. ALK positivity was 12.2% by IHC and confirmed at 8.2% of tumors by FISH, with complete concordance between IHC 3+/0 and FISH+/- assessments, respectively. Five-year risk of progression or recurrence was doubled for patients with ALK-positive compared with ALK-negative tumors; ALK-positive tumors also appeared to be associated with a higher risk of brain and liver metastases.
Conclusions: Our findings suggest that ALK positivity is associated with a significantly poor outcome in nonsmoking-related adenocarcinoma and that ALK-positive tumors may be associated with an increased risk of brain and liver metastases compared with ALK-negative disease. Consequently, an unmet medical need exists in ALK-positive lung cancer patients, and effective ALK-specific therapies are needed.
Conflict of interest statement
Conflicts of interest: KK is an employee of Pfizer, Inc.
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Source: PubMed