033. Defining the role of tyrosine kinase inhibitors in early stage non-small cell lung cancer

Objective: Historical, the non-small cell lung cancer (NSCLC) was as a united disease entity and the chemotherapy to the metastastic cancer had limited results. Recent studies for the metastastic NSCLC led to the ascertainment that the NSCLC does not constitute exclusively a disease entity, but different neoplasms guided from different molecular paths, different biological behavior and at extension requires different confrontation. Thus the new direction for the therapeutic approach of NSCLC is henceforth the most individualised approach based on the activated molecular paths of tumour. Distinct subtypes of NSCLC are driven by a specific genetic alteration, like EGFR, ALK, ROS1 or BRAF mutations, and are thus sensitive to inhibition of the corresponding activated oncogenic pathway.

Material and methods: The benefit from the use of tyrosine kinase inhibitors in patients with EGFR mutations it was confirmed by six randomised studies of phase III that investigated the role of gefitinib, erlotinib and afatinib.

Results: In these studies those response rates oscillated in the impressive percentages from 55% to 86% and were connected with a remarkable median progression free survival of approximately 8 to 13 months, and with better quality of life compared to that of chemotherapy.

Conclusions: In early stages NSCLC is needed the individualization of systemic treatment in order to reduce toxicity that is observed in the classic chemotherapy and to impact outcome. The role of EGFR TKI's has been evaluated in the adjuvant chemotherapy in early stage resected NSCLC. The data from these studies suggest that adjuvant TKI therapy might not increase the overall survival, but delay the recurrences. 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. This period is ongoing prospective trials that may offer the opportunity for a definitive answer of the role of tyrosine kinase inhibitors in induction treatment before chemoradiotherapy or in early disease adjuvant therapy.

Keywords: Lung cancer; EGFR; Iressa; Tarceva