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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.S. Shim
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).
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
P1.02-030 - Performance Evaluation of ALK/ROS1 Dual Break Apart FISH Probe Kit (RUO) in Non-Small-Cell Lung Cancer (ID 5233)
14:30 - 15:45 | Author(s): H.S. Shim
ALK and ROS1 gene rearrangements are distinct molecular subsets of non-small-cell lung cancer (NSCLC), and they are strong predictive biomarkers of response to ALK/ROS1 inhibitors, such as crizotinib. Thus, it is clinically important to detect patients who will benefit from such treatment and develop an effective screening strategy. In this study, we aim to evaluate the diagnostic performance of ALK/ROS1 RUO FISH probes which can concurrently detect ALK and ROS1 rearrangements.
The study populations were composed of three patient cohorts with histologically confirmed lung adenocarcinoma (ALK rearrangement, ROS1 rearrangement and both wild type). Patient specimens consisted of 12 ALK-positive, 9 ROS1-positive and 21 ALK/ROS1-wild type formalin-fixed paraffin-embedded samples obtained from surgical resection or excisional biopsy. ALK rearrangement status was determined by Vysis LSI Dual Color Break Apart Rearrangement Probe (Abbott Molecular, Abbott Park, IL, USA) and ROS1 rearrangement status was assessed by ZytoLight SPEC ROS1 dual color break apart probe (Zytovision. Bremerhaven, Germany). All specimens were re-evaluated by ALK/ROS1 Break Apart FISH RUO 4-color kit. FISH images were scanned via the BioView Duet and interpreted remotely via BioView SoloWeb.
A total of 42 patient samples were evaluated. The concordance of results obtained from ALK/ROS1 Break Apart FISH RUO 4-color kit was evaluated relative to the ALK and ROS1 rearrangement status of the specimen, as previously determined. One ROS1-positive and 2 wild-type samples were excluded from analysis due to high background. Regarding 12 ALK-positive samples, 12 were ALK-positive by ALK/ROS1 RUO FISH, showing 100% (n=12/12) sensitivity to predict ALK rearrangement. Regarding 8 ROS1-positive samples, 6 cases were ROS1-positive by ALK/ROS1 RUO FISH, showing 75% (n=6/8) sensitivity to predict ROS1 rearrangement. Two cases showed weak ROS1 signals that could not be enumerated. Regarding 19 wild type cases, 18 cases were negative by ALK/ROS1 RUO FISH, showing 95% (n=18/19) specificity, while one case showed poor ROS1 signals which could not be properly enumerated.
ALK/ROS1 RUO FISH can detect ALK and ROS1 rearrangements simultaneously in NSCLC. The fluorescence of ROS1 signal may be weakened by slide shipment and remote scoring.