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MA07 - ALK-ROS1 in Advanced NSCLC (ID 385)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
MA07.07 - Ceritinib in ROS1-Rearranged Non-Small-Cell Lung Cancer: An Update of Korean Nationwide Phase II Study (ID 5953)
11:00 - 12:30 | Author(s): H.R. Kim
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) was performed in available tumor samples. Ceritinib 750mg was administered once daily and 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 and IHC. ROS1 fusion partners were identified with the use of next-generation sequencing (NGS) in available tumor samples.
Between June 7, 2013, and February 1, 2016, a total of 404 patients underwent ROS1 prescreening, and 32 ROS1+ (by FISH) patients were enrolled. All patients except two (who did not respond to ceritinib) were crizotinib naïve. The median age of all patients was 62 years, and there were 24 females (75%). The majority of patients (84%) were never smokers, and all had adenocarcinoma histology. The median number of previous treatments before study enrollment 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. Of the 32 patients enrolled, 28 patients were evaluable for response by independent radiologic review. 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), with 17 (53%) patients still in follow-up for progression. 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 (vomiting, nausea, diarrhea) 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 (ClinicalTrials.gov number, NCT01964157).