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MA07 - ALK-ROS1 in Advanced NSCLC (ID 385)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
MA07.05 - EUCROSS: A European Phase II Trial of Crizotinib in Advanced Adenocarcinoma of the Lung Harboring ROS1 Rearrangements - Preliminary Results (ID 4451)
11:00 - 12:30 | Author(s): R. Buettner
ROS1 rearrangements are present in the tumors of 1-2% of patients with lung adenocarcinoma (LAD). This patient subgroup is characterized by non-smoking history and younger than average age compared to the overall NSCLC population. In a phase I trial the ALK/ROS1/MET inhibitor crizotinib has shown to be highly effective in these patients (NCT00585195). EUCROSS is a prospective phase II trial of the Lung Cancer Group Cologne in collaboration with the Spanish Lung Cancer Group to evaluate crizotinib in ROS1-positive LAD. Here, we present preliminary data on efficacy and safety.
Patients with advanced LAD harboring ROS1 rearrangements as confirmed by central FISH were eligible for the trial irrespectively of the number of prior treatment lines. Patients received treatment with crizotinib 250 mg BID - doses were adapted for management of AEs. Trial design: Fleming’s single stage phase II design. Primary endpoint: ORR (95% CI, H~0~: ORR≤20% vs. H~1~: ORR>20%). Secondary endpoints: a.o. PFS, OS and safety. All efficacy endpoints were assessed by investigator’s RECIST v1.1 and will be analyzed by IRB at a later stage. Baseline tumor tissue was analyzed by DNA-sequencing to identify the translocation Partners of ROS1, to validate FISH results and to identify additional biomarkers for prediction of response. Data-cut off for this report was March 2016.
In total, 34 patients were enrolled in EUCROSS at the time of data cut-off. Twenty-nine patients were eligible for efficacy assessment. Tumor tissue of 20 of these patients was suitable for further sequencing - 18 were sequenced positive for ROS1 fusion. The fusion partners involved were CD74 (N=9;50%), EZR (N=4;22%), SCL34A2 (N=3;17%), TPM3 and SDC4(N=1;6% each). The investigator assessed ORR was 69% (95% CI, 49.1-84.3) in the overall trial population and 83% (95% CI, 67.7-94.2) in the ROS1-positive by sequencing population (N=18;P=0.324 for difference of ORR). Three patients (10.3%;95% CI, 3.6-26.4) exhibited primary progression, two of them were sequenced ROS1-negative. All patients were included in the safety population (N=34). Most common AEs irrespectively of relatedness or grade were visual disorders (N=16;48%), edema (N=14;41%), diarrhea (N=13;38%) and bradycardia (N=11;32%).
Crizotinib is a highly effective and safe treatment in the subset of ROS1 rearranged NSCLC patients as determined by FISH and DNA-sequencing. Although, the number of patients with tissue available for sequencing was low at the time of data cut-off, sensitivity and specificity support sequencing as the potential new gold-standard for the identification of clinically relevant ROS1 gene-rearrangements.
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
P2.03b-028 - Improved Overall Survival Following Implementation of NGS in Routine Diagnostics of Advanced Lung Cancer in Germany: Results of the NGM (ID 5304)
14:30 - 15:45 | Author(s): R. Buettner
Broad implementation of molecular diagnostics and personalized cancer care is hampered by insufficient molecular screening, missing reimbursement for comprehensive molecular testing and lack of access to appropriate drugs. The Network Genomic Medicine (NGM) Lung Cancer is a health care provider network offering comprehensive next generation sequencing (NGS)-based multiplex genotyping on a central diagnostics platform in Cologne for all inoperable lung cancer patients (pts) in Germany.
The NGS panel used in NGM consists of 14 genes and 102 amplicons to cover potentially targetable aberrations. Mutation analyses were run on an Illumina (MySeq) platform, while FISH analyses were performed separately. In 2015, we have started the second outcome evaluation for all NGM pts who had received NGS-based molecular diagnostics. In particular, we have focused on molecular subgroups of EGFR, ALK, BRAF-V600E, HER2 and ROS1 positive pts and especially on NGM pts treated in clinical trials.
From 2013-2015 6210 lung cancer pts (n=4244 non-squamous NSCLC) were genotyped. Preliminary data show the overall survival (OS) of 934 NSCLC pts including of 110 NSCLC pts treated in clinical trials. For 108 EGFR+ pts, the OS of clinical trials pts treated with so called 3[rd] generation EGFR-TKIs was 55 months (n=25) vs 22 months in control group (n=83) (p=0,002; mean OS: 29 months; 95%CI: 36-83 months). For 85 ALK+ pts, the OS of pts treated in clinical trials was 35 months (n=19) compared to OS of 23 months for 45 pts treated with one ALK inhibitor and 8 months for 19 pts treated with no ALK inhibitors (P<0,0001; mean OS: 22 months; 95%CI: 22-33 months).
While the first NGM evaluation in 2013 already showed a survival benefit of 2 years in EGFR-TKI treated EGFR+ pts compared to chemotherapy, our current evaluation in pts treated with 3[rd] generation EGFR-TKIs after acquired resistance to 1[st] gen. EGFR-TKIs shows the significant increasing of the OS. Similarly, we show a significant longer OS for ALK+ pts treated with 2 ALK inhibitors compared to treatment with one or no ALK inhibitor. Further results of this ongoing NGM evaluation will be provided.