J Cancer 2015; 6(6):568-574. doi:10.7150/jca.11893


Defining the Role of Tyrosine Kinase Inhibitors in Early Stage Non-Small Cell Lung Cancer

Sofia Lampaki1, George Lazaridis2, Konstantinos Zarogoulidis1, Ioannis Kioumis1, Antonis Papaiwannou1, Katerina Tsirgogianni1, Anastasia Karavergou1, Theodora Tsiouda3, Vasilis Karavasilis3, Lonny Yarmus4, Kaid Darwiche5, Lutz Freitag5, Antonios Sakkas6, Angeliki Kantzeli7, Sofia Baka8, Wolfgang Hohenforst-Schmidt9, Paul Zarogoulidis1✉

1. Pulmonary Department-Oncology Unit, “G. Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece,
2. Department of Medical Oncology, “G. Papageorgiou” University Hospital, Thessaloniki, Greece, Nea Eukarpia.
3. Pulmonary Department, “Theageneio Anticancer” Hospital, Thessaloniki, Greece, Alexander Simeonidi 2
4. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, U.S.A.
5. Department of Interventional Pulmonology, Ruhrlandklinik, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
6. Department of Internal Medicine, “Evangelisches Krankenhaus”, Mülheim, Germany
7. Department of Internal Medicine, “Helios Klinikum”, Wuppertal, Germany
8. Oncology Department, “Interbalkan” European Medical Center, Thessaloniki, Greece
9. Medical Clinic I, ''Fuerth'' Hospital, University of Erlangen, Fuerth, Germany

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Lampaki S, Lazaridis G, Zarogoulidis K, Kioumis I, Papaiwannou A, Tsirgogianni K, Karavergou A, Tsiouda T, Karavasilis V, Yarmus L, Darwiche K, Freitag L, Sakkas A, Kantzeli A, Baka S, Hohenforst-Schmidt W, Zarogoulidis P. Defining the Role of Tyrosine Kinase Inhibitors in Early Stage Non-Small Cell Lung Cancer. J Cancer 2015; 6(6):568-574. doi:10.7150/jca.11893. Available from http://www.jcancer.org/v06p0568.htm

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Historical, the non-small cell lung cancer (NSCLC) was as a united disease entity and the chemotherapy to the metastatic cancer had limited results. Recent studies for the metastatic non-small cell lung cancer 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 individualized approach based on the activated molecular paths of tumor. Distinct subtypes of NSCLC are driven by a specific genetic alteration, like EGFR, ALK, ROS1 or BRAF mutations, and these genetic alterations are sensitized to the inhibition of specific oncogenic pathways. The benefit from the use of tyrosine kinase inhibitors in patients with EGFR mutations it was confirmed by six randomized studies of phase III that investigated the role of gefitinib, erlotinib and afatinib. In these studies the response rates vary 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. 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 chemo-radiotherapy (RTOG 1210/Alliance 31101), are ongoing. Ongoing prospective trials may offer the opportunity for a definitive answer of the role of tyrosine kinase inhibitors in induction treatment before chemo-radiotherapy or in early disease adjuvant therapy.

Keywords: lung cancer, egfr, iressa, tarceva