P88.02 SDC4-ROS1 Fusion as a Mechanism of Acquired Resistance in EGFR-Mutant Lung Adenocarcinoma

Abstract

The enhanced understanding of the biological mechanisms underlying non-small cell lung cancer (NSCLC) development and progression has led to targeted therapies becoming an increasingly important strategy for the treatment of NSCLC. Several clinical trials have demonstrated that most NSCLC patients with specific epidermal growth factor receptor (EGFR) mutations respond significantly to EGFR tyrosine kinase inhibitors (TKIs). However, the majority of patients who initially respond to EGFR-TKI therapies eventually develop drug resistance, often within a year. The subsequent development of T790M mutations occurs in roughly half of EGFR-mutant patients who develop EGFR-TKI resistance. Herein we present a 37-year-old never-smoker Chinese female with an EGFR exon 19 deletion who was diagnosed with lung adenocarcinoma (LADC) and initially responded to first-generation EGFR-TKI treatment, later developing acquired resistance. The subsequent biopsy specimen was subjected to next generation sequencing (NGS) and a SDC4-ROS1 rearrangement was detected. The patient received crizotinib therapy and was considered to have a partial response. The progression free survival was 16.0 months. To our knowledge, SDC4-ROS1 fusion gene as a novel mechanism of acquired EGFR resistance in lung adenocarcinoma is the first reported in China. In the future, the routine use of next generation sequencing is important, more and more ROS1 fusions are identified in lung cancer by next generation sequencing.