69IN - Defining the Role of Targeted Therapies in Early Stage Non-Small Cell Lung Cancer (Nsclc)

Abstract

ABSTRACT Disseminated micrometastatic disease often limits the effectiveness of aggressive locoregional treatment strategies in stage I-III NSCLC. Perioperative chemotherapy results in a minimal survival advantage at the cost of significant toxicity in a subgroup of patients. Concomitant chemotherapy improves radiotherapy treatment outcome in locally advanced NSCLC, however remaining associated with a dismal prognosis. Distinct subtypes of NSCLC are driven by a specific genetic alteration and are thus sensitive to inhibition of the corresponding activated oncogenic pathway. This new paradigm has substantially impacted advanced NSCLC treatment. Treatment of patients with EGFR activating and sensitizing mutations-driven NSCLC with EGFR tyrosine kinase inhibitors (TKIs) results in an unprecedented response rate of 60-80%, a median progression free survival of approximately 8-13 months, as well as an improved quality of life compared to chemotherapy. Tumor genotype analysis has to date identified driver alterations in approximately 50% to 80% of NSCLC patients according to demographics, and particularly ethnicity. In early stages NSCLC, individualization of systemic treatment is needed to reduce toxicity and to impact outcome. The role EGFR TKIs in the perioperative setting has been evaluated in early stage resected NSCLC. Despite a potential disease free survival benefit in early stage was suggested in a retrospective study from the Memorial Sloan Kettering Cancer Center, data of the prospective RADIANT trial do not allow concluding about an increase in the cure rate related to the use of adjuvant EGFR TKIs in early NSCLC. Data from adjuvant studies suggest that adjuvant TKI therapy might not increase cure rate, but simply delay recurrences. Currently, data on the use of gefitinib as a consolidation treatment after or cetuximab together with chemoradiotherapy in unselected locally advanced stage III are disappointing. Prospective trials restricted to EGFR or ALK driven NSCLC subsets potentially offering the opportunity for a definitive answer in early disease adjuvant setting (ALCHEMIST) or as induction treatment before stage III chemoradiotherapy (RTOG 1210/Alliance 31101), are ongoing. Disclosure: The author has declared no conflicts of interest.