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KIF 5 B & CCDC 6 RET in Lung Cancer: Clinical Insights and Response KIF 5 B & CCDC 6 RET in Lung Cancer: Clinical Insights and Response to Personalized Based Therapy 1, A. Moore 1, M. Gottfried 2, R. Katznelson 3, H. Nechushtan 4, M. Wollner 5, V. Neiman 1, L. Soussan-Gutman 6, A. Dvir 6, N. Peled 1 M. Sarfaty 1 Institute of Oncology, Davidoff Center, Rabin Medical Center, Petach Tikva, Tel Aviv University, Tel Aviv, Israel; 2 Institute of Oncology, Meir Medical Center, Kfar Saba, , Tel Aviv University, Tel Aviv, Israel; 3 Institute of Oncology, Kaplan Medical Center, Rehovot, Hebrew University, Jerusalem, Israel; 4 Sharett Institute of Oncology, Hadassah Medical Center, Hebrew University, Jerusalem, Israel; 5 Institute of Oncology, Rambam Health Care Campus, Technion Israel Institute of Technology, Haifa, Israel; and 6 Oncotest-Teva Pharmaceutical Industries, Petach Tikva, Israel. Introduction: Complete response to cabozantinib: Ø RET mutations are found in 1 -2% of ADC NSCLC Ø 70 -90% KIF 5 B-RET fusion Ø 10 -25% CCDC 6 -RET fusion Ø The natural history and management of RET mutated lung cancer are still unclear. Ø The KIF 5 B subtype showed an aggressive presentation. Ø One patient (KIF 5 B-RET) treated by cabozantinib 140 mg/day showed a rapid and durable complete response by RECIST Criteria for 8 months. Ø Grade III adverse -palmar plantar erythrodysesthesia and dysphagia. Ø To our knowledge, this is the first report of a complete response to cabozantinib for this indication. Methods: Ø A multicenter, retrospective, descriptive report of eight RET-mutated lung cancer patients, diagnosed between May 2009 and January 2015. Results: No. Sex Age Smoking (y) (PY) 1 F 50 Never Stage at Diagnosis IV RET subtype Treatment Response duration for 1 st line, m (Response) 0 (PD) KIF 5 B Chemo 2 F 48 20 IV KIF 5 B Cabozantinib 8 (CR) 3 F 65 3 IV CCDC 6 Chemo+Bev 9 (PR) 4 M 62 Never IA CCDC 6 Surgery NR (NED) 5 M 28 Never IV KIF 5 B Chemo 7 (PR) 6 M 39 10 IV CCDC 6 Chemo 2 (PD) 7 M 44 Never IIA KIF 5 B Chemo 8 (PR) 8 F 72 2 IV KIF 5 B Chemo 4 (PR) Conclusions : Ø RET-fusion LADC may have an abrupt and acute presentation; in our series, tend to be associated with KIF 5 B subgroup. Ø While some RET-fusion positive LADC patients might benefit from combination chemotherapy, it may also be that the most effective targeted therapy is cabozantinib with a potential long standing complete response. Acknowledgment: Ø Maya Ilouze, Ph. D Ø Champions Oncology Correspondence: Prof Nir Peled; [email protected] tau. ac. il