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Predictive and Prognostic Value of ALK Gene Rearrangement in Non- Small Cell Lung Cancer

Kimary Kulig, Yi Wang, Shrividya Iyer and Ping Yang

Anaplastic Lymphoma Kinase (ALK) is a relatively new as an oncogenic driver and a therapeutic target in Non-Small Cell Lung Cancer (NSCLC); the prognostic and predictive implications of ALK-positivity in NSCLC is far from clear and no large-scale studies have been reported to date. In the current review, we summarize published data examining the variation in prognostic and predictive effect of ALK-positivity on clinical outcomes in NSCLC patients, based on the extent of control of or adjustment for known confounding factors such as smoking status, disease stage, and age by study design or analyses. ALK rearrangement in NSCLC did not appear to be predictive of improved outcomes with chemotherapy but was predictive of poor response to EGFR TKI therapy. Overall, ALK rearrangement was found to be a negative prognostic factor in NSCLC in studies controlling for known confounding factors. In addition to highlighting the importance of controlling for confounding factors in retrospective studies evaluating outcomes, our review also summarizes evidence of an unmet need in terms of poor response amongst ALK-positive NSCLC patients to standard therapies that do not target ALK.