SUMMARY: Lung cancer is the second most common cancer in both men and women and accounts for about 13% of all new cancers and 27% of all cancer deaths. It is the leading cause of cancer death among both men and women. The American Cancer Society estimates that over 221,200 new cases of lung cancer will be diagnosed in the United States in 2015 and over 158,000 patients will die of the disease. Non-Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all lung cancers. Of the three main subtypes of Non Small Cell Lung Cancer (NSCLC), 25% are Squamous cell carcinomas, 40% are Adenocarcinomas and 10% are Large cell carcinomas. There is now growing body of evidence suggesting superior outcomes when advanced NSCLC patients with specific genomic alterations receive targeted therapies.
Approximately 1% – 2% of lung adenocarcinomas harbor ROS1 gene rearrangements. ROS1 gene is located on chromosome 6q22 (long arm of chromosome 6) and plays an important role in cell growth and development. ROS1 gene fusion with another gene results in a mutated DNA sequence which then produces an abnormal protein responsible for unregulated cell growth and cancer. ROS1 gene rearrangement has been identified as a driver mutation in Non Small cell Lung Cancer with adenocarcinoma histology. This is more common in nonsmokers or in light smokers (<10 pack years) who are relatively young (average age of 50 years) and thus share similar characteristics with ALK-positive patients. The ROS protein and the ALK protein have similar structure and function and are sensitive to Tyrosine Kinase Inhibitors such as XALKORI® (Crizotinib) and ZYKADIA® (Ceritinib). ROS1 mutations have been also been associated with Cholangiocarcinoma (Bile duct cancer) and Glioblastoma multiforme. ROS1 rearrangements are mutually exclusive with other oncogenic mutations found in NSCLC such as EGFR mutations, KRAS mutations and ALK rearrangement. The presence of a ROS1 rearrangement can be detected by Fluorescence In Situ Hybridization (FISH), ImmunoHistoChemistry (IHC), Reverse Transcriptase– Polymerase Chain Reaction (RT-PCR) and Next Generation-Sequencing. XALKORI® is a small molecule Tyrosine Kinase Inhibitor that targets ALK, MET and ROS1 tyrosine kinases. In a previously published expansion cohort of the phase 1 study by Shaw and colleagues ( NEJM 2014; 371:1963-1971), XALKORI® showed significant activity in patients with in patients with advanced ROS1rearranged NSCLC. The authors in this publication provided additional evidence that ROS1 gene rearrangement is an actionable target in NSCLC, by conducting a retrospective study in centers that tested for ROS1 rearrangement and evaluated the outcomes of ROS1-positive NSCLC patients, who had been treated with XALKORI®. They included 32 patients with NSCLC whose tumors showed ROS1 rearrangement and who had received off-label treatment with XALKORI®. The median age was 50.5 years. They noted an overall response rate of 80% and a disease control rate, 86.7%. The median Progression Free Survival (PFS) was 9.1 months, and the PFS rate at 12 months was 44%. This impressive efficacy data again validates that similar to EGFR mutations and ALK rearrangements, ROS1 gene rearrangements are molecular drivers and patients with NSCLC with adenocarcinoma histology should be tested for ROS1. Crizotinib Therapy for Advanced Lung Adenocarcinoma and a ROS1 Rearrangement: Results From the EUROS1 Cohort. Mazières J, Zalcman G, Crinò L, J Clin Oncol. 2015;33:992-999
Bottom Ad
Advertisement
Subscribe
