1205PD - Ceritinib in ROS1-rearranged non-small-cell lung cancer: a Korean nationwide phase II study

Date 09 October 2016
Event ESMO 2016 Congress
Session NSCLC, metastatic
Topics Anticancer Agents
Non-Small Cell Lung Cancer
Biological Therapy
Presenter Sun Min Lim
Citation Annals of Oncology (2016) 27 (6): 416-454. 10.1093/annonc/mdw383
Authors S.M. Lim1, B.C. Cho2, H.R. Kim3, J. Lee4, K.H. Lee5, Y. Lee6, Y.J. Min7, E.K. Cho8, S. Lee9, B. Kim10, M.Y. Choi11, H.S. Shim12, J.H. Chung13, Y.L. Choi14, M.J. Lee15, M. Ahn16
  • 1Medical Oncology, CHA Bundang Medical Center, 120752 - Gyeonggi-do/KR
  • 2Internal Medicine, Yonsei Severance Hospital Cancer Center, 120752 - Seoul/KR
  • 3Internal Medicine, Yonsei Severance Hospital Cancer Center, Seoul/KR
  • 4Medical Oncology, Seoul National University Bundang Hospital, Seongnam-si/KR
  • 5Medical Oncology, Chungbuk National University Hospital, Cheong-ju/KR
  • 6Medical Oncology, Kangbuk Samsung Hospital Sungkyunkwan University, Seoul/KR
  • 7Medical Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KR
  • 8Medical Oncology, Gachon University Gil Hospital, Incheon/KR
  • 9Medical Oncology, Inje University Haeundae Paik Hospital, Busan/KR
  • 10Medical Oncology, Veterance Hospital, Seoul, Seoul/KR
  • 11Medical Oncology, Inje University Busan Paik Hospital, Busan/KR
  • 12Pathology, Yonsei Cancer Center Yonsei University, Seoul/KR
  • 13Pathology, Seoul National University Bundang Hospital, Seongnam-si/KR
  • 14Pathology, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul/KR
  • 15Medical Oncology, Yonsei Cancer Center, Seoul/KR
  • 16Medical Oncology, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul/KR



ROS1 rearrangement is a distinct molecular subset of non-small-cell lung cancer (NSCLC). We investigated the efficacy and safety of ceritinib in patients with ROS1-rearranged NSCLC.


We enrolled 32 patients with advanced NSCLC who tested positive for ROS1 rearrangement by fluorescent in situ hybridization (FISH). ROS1 immunohistochemistry (IHC) and next-generation sequencing (NGS) were performed in available tumor samples. The primary endpoint was objective response rate (ORR) by central independent radiologic review. The secondary endpoints included disease control rate (DCR), duration of response, progression-free survival (PFS), overall survival (OS), toxicity and concordance between FISH, IHC and NGS.


Between June 7, 2013, and February 1, 2016, a total of 404 patients underwent ROS1 prescreening, and 32 ROS1+ (by FISH) patients were enrolled. The median age of all patients was 62 years, and the majority of patients (84%) were never smokers, and all had adenocarcinoma histology. The median number of previous treatments was 3 (range, 2-7) and 17 (53%) patients had received three or more lines of chemotherapy. At the time of the data cut-off (April 18, 2016), the median follow-up was 7.5 months, and 15 (47%) patients had discontinued treatment. The ORR was 63% (95% CI, 45.7-79.3), with 1 complete response and 19 partial responses. The median duration of response was 10.0 months (range, 0.4 + -18.4+). Among 11 tumors that were tested by NGS, we identified 7 ROS1 fusion partners including ROS1-CD74, ROS1-SLC34A2, and ROS1-EZR. The median progression-free survival was 19.3 months (95% CI, 7.2-not reached), and the median overall survival was not reached at the time of the data cut-off. Of 5 patients with retrospectively confirmed brain metastases, intracranial disease control was reported in 4 patients (80%). Gastrointestinal adverse events, mostly grade 1-2, were the most frequent adverse events (80%); these events were manageable.


Ceritinib demonstrated potent clinical activity in patients with advanced, ROS1-rearranged NSCLC, who received at least one prior line of platinum-based chemotherapy. ROS1 rearrangement defines a second molecular subgroup of NSCLC for which ceritinib is highly active.

Clinical trial identification


Legal entity responsible for the study



Novartis Pharmaceutical


All authors have declared no conflicts of interest.