JS3-2 - Nimotuzumab in Combination with Concurrent Chemoradiotherapy (CRT) in Patients with Locally Advanced Non-Small-Cell Lung Cancer (NSCLC)

Abstract

ABSTRACT The standard of treatment of stage III locally advanced, inoperable, non-small-cell lung cancer (NSCLC) is concurrent chemoradiotherapy (CRT) using platinum-based regimen. Recently, researchers have been testing to see whether targeted therapy in combination with CRT might prove beneficial. The epidermal growth factor receptor (EGFR) is over-expressed in a wide variety of human tumors, including NSCLC. EGFR expression is also correlated with alterations in cell cycle progression, increased tumor cell invasiveness, enhanced angiogenesis, and decreased apoptosis of tumor cells. Overexpression of EGFR in tumors correlates with increased metastasis, decreased survival, and a poor prognosis. Radiation activates EGFR autophosphorylation and increases the activity of protein tyrosine kinase. Thus radiation predominantly activates EGFR and thereby initiates downstream processes leading to radioresistance. Repeated radiation exposures modulate the expression of EGFR. Treatment of locoregionally advanced head and neck cancer with concomitant radiotherapy plus cetuximab, an anti-EGFR mAb, improves locoregional control and reduces mortality. While nimotuzumab has similar preclinical and clinical activity when compared with other anti-EGFR mAbs in certain indications, nimotuzumab has one major difference, the lack of severe skin toxicity. In vitro studies have demonstrated that nimotuzumab increases the radiosensitivity of NSCLC cell lines. When administered in combination with radiotherapy, nimotuzumab is expected to increase locoregional control and reduce mortality. In this presentation, I would like to introduce the clinical study results and future perspectives of nimotuzumab in combination with concurrent CRT in patients with locally advanced NSCLC.