83IN - New Strategies on the Horizon

Abstract

ABSTRACT Since the discovery of activating epidermal growth factor receptor (EGFR) mutation in 2004, personalized therapy for patient with advanced non-small lung cancer (NSCLC) has become a reality. EGFR TKI and ALK inhibitor are standard treatment for pt with the target. Mutational status of signalling genes is key to management of lung cancer. Base on this principles, there are a number of new treatment strategy on horizon. Clinical application of genome profiling is a strategy that may improve the outcome of personalized therapy. Population genome profiling has provided important information on patients with adenocarcinoma. A number of population based genome profile from patients with adenocarcinoma in USA, France, China and Japan have been reported. EGFR mutation is more common in Asian population while KRAS mutation is much less common. Other mutations on ALK, BRAF, HER-2, PI3K, or MET are less frequent and similar across population. Future strategy will be personal genome profiling. With the improvement in efficiency and reduction in cost of second-generation sequencer, it will be feasible and practical to formulate treatment strategy according to genome profile. However, genome profile may vary over time and between tumors. Genomic heterogeneity must be addressed if attempt is comprehensive control of all tumor sites by a single targeted therapy. Gerlinger et al (NEJM 366:883, 2012) performed extensive exome sequencing from multiple site of renal cells tumor and its metastasis, and found 63 to 69% of somatic mutations are not consistently present in all tumor regions. Intra-tumor heterogeneity included the mTOR gene which is the primary target for approved therapy such as everolimus. Thus authors concluded that single site needle biopsy may not be representative of the genomic status of the tumor. Other examples including pancreatic cancer and breast cancer also review similar heterogeneity. There is no reason to believe lung cancer to be different. New strategy must be form to address tumor heterogeneity. In summary, new treatment strategies included individualized genome profiling and study of tumor heterogeneity. More specifically there should be upcoming treatment strategy for KRAS mutation and squamous cell carcinoma. Disclosure T.S.K. Mok: Consultancy with Astrazeneca, Roche, Pfizer, Eli Lilly, Merck Serono, Beigene, Eisai, Jannsen, Taiho Speaker engagment with Astrazeneca, Roche, Pfizer, Eli Lilly, Merck Serono