EGFR-TKIs in adjuvant treatment of lung cancer: to give or not to give?

Aleksandar Milovancev,1 Vladimir Stojsic,1 Bojan Zaric,1 Tomi Kovacevic,1 Tatjana Sarcev,1 Branislav Perin,1 Konstantinos Zarogoulidis,2 Katerina Tsirgogianni,2 Lutz Freitag,3 Kaid Darwiche,3 Drosos Tsavlis,2 Athanasios Zissimopoulos,4 Grigoris Stratakos,5 Paul Zarogoulidis2 1Institute for Pulmonary Diseases of Vojvodina, Clinic for Thoracic Oncology, Faculty of Medicine, University of Novi Sad, Serbia; 2Pulmonary Department-Oncology Unit, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3Department of Interventional Pneumology, Ruhrlandklinik, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; 4Nuclear Medicine Department, Democritus University of Thrace, Alexandroupolis, 5Department of Interventional Pneumology, “Sotiria” Hospital of Chest Diseases, Athens, Greece Abstract: Epidermal growth factor receptor-tyrosine-kinase inhibitors (EGFR-TKIs) brought a significant revolution in the treatment of non-small-cell lung cancer (NSCLC). In a short period of time, EGFR-TKIs became the standard of treatment for mutation-positive, advanced stage non-squamous NSCLC. In recent years, second- and third-generation EGFR-TKIs are emerging, further widening the clinical use. However, the question of EGFR-TKIs efficiency in the treatment of early stage NSCLC still remains open. Early clinical trials failed to approve the use of EGFR-TKIs in adjuvant setting. The majority of these early trials were performed in unselected NSCLC populations and without standardized biomarker identification. One should certainly not rely solely on these results and dismiss the use of EGFR-TKIs as adjuvant therapy. Many important questions are still unanswered. Most important issues such as stage heterogeneity (IA–IIIA), timing (after or concomitantly with chemotherapy), and type of administration (monotherapy or combination) need to be answered in near future. Adjuvant TKIs in the tr