Neoadjuvant, Adjuvant and Perioperative Treatment in Early-Stage Non-Small Cell Lung Cancer (NSCLC) with Actionable Genomic Alterations: Current Landscape and Future Perspectives

Abstract

Surgical resection remains the cornerstone of curative-intent treatment for both oncogene and non-oncogene addicted early-stage non-small cell lung cancer, with neoadjuvant/adjuvant chemotherapy providing only a modest benefit in terms of disease-free survival and overall survival. Currently, in non-small-cell lung cancer without actionable molecular alterations, the addition of neoadjuvant or perioperative immunotherapy to chemotherapy has become the standard of care for resectable disease, with significant improvements in the rates of complete pathological response, major pathological response, and event-free survival. In terms of oncogene-addicted non-small-cell lung cancer, adjuvant treatment of completely resected disease with the third-generation EGFR inhibitor osimertinib in patients harboring activating EGFR mutations or the second-generation ALK inhibitor alectinib in patients with an ALK fusion/translocation has brought about a paradigm shift by significantly improving event-free survival and, in the case of osimertinib, overall survival. A glimpse into the future management of patients with early-stage disease and a common EGFR mutation or an ALK fusion/translocation may reveal a perioperative use of the respective targeted treatment. Data for the rest of the actionable molecular alterations remain limited, and those tumors are usually treated with algorithms used for non-oncogene-addicted non-small-cell lung cancer. This review aims to summarize all existing evidence about the current management of patients with early-stage non-small-cell lung cancer and actionable molecular alterations and to examine the future directions in this rapidly evolving field.