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M. Takeda
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MA08 - Treatment Monitoring in Advanced NSCLC (ID 386)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:R. Perez-Soler, T. Reungwetwattana
- Coordinates: 12/06/2016, 11:00 - 12:30, Lehar 3-4
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MA08.10 - Detection of the T790M Mutation of EGFR in Plasma of Advanced NSCLC Patients with Acquired Resistance to EGFR-TKI (WJOG8014LTR) (ID 5377)
12:06 - 12:12 | Author(s): M. Takeda
- Abstract
- Presentation
Background:
NSCLC patients with activating mutations of the EGFR initially respond well to TKIs, but about half such patients develop TKI resistance through acquisition of a secondary T790M mutation. Whereas next-generation EGFR-TKIs have been developed to overcome T790M-mediated resistance, performance of a second tumor biopsy to assess T790M mutation status can be problematic.
Methods:
We developed and evaluated liquid biopsy assays for detection of TKI-sensitizing and T790M mutations of EGFR by droplet digital PCR (ddPCR) in EGFR mutation–positive patients with acquired EGFR-TKI resistance.
Results:
A total of 260 patients was enrolled between November 2014 and March 2015 at 29 centers for this West Japan Oncology Group (WJOG 8014LTR) study. Plasma specimens from all subjects as well as tumor tissue or malignant pleural effusion or ascites from 41 patients were collected after the development of EGFR-TKI resistance. All plasma samples were genotyped successfully and the results were reported to physicians within 14 days. TKI-sensitizing and T790M mutations were detected in plasma of 120 (46.2%) and 75 (28.8%) patients, respectively. T790M was detected in 56.7% of patients with plasma positive for TKI-sensitizing mutations. For the 41 patients with paired samples obtained after acquisition of EGFR-TKI resistance, the concordance for mutation detection by ddPCR in plasma compared with tumor tissue or malignant fluid specimens was 78.0% for TKI-sensitizing mutations and 65.9% for T790M.
Conclusion:
Noninvasive genotyping by ddPCR with cell-free DNA extracted from plasma is a promising approach to the detection of gene mutations during targeted treatment.
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OA23 - EGFR Targeted Therapies in Advanced NSCLC (ID 410)
- Event: WCLC 2016
- Type: Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:O.T. Brustugun, S. Lu
- Coordinates: 12/07/2016, 14:20 - 15:50, Stolz 2
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OA23.06 - Overall Survival (OS) of EGFR Mutation Positive Non-Small Cell Lung Cancer Patients: Real-World Treatment Patterns of 1,660 Japanese Patients (ID 5915)
15:15 - 15:25 | Author(s): M. Takeda
- Abstract
- Presentation
Background:
Since the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) was launched in Japan, the survival periods of advanced/recurrent EGFR mutation positive (EGFR m+) non-small cell lung cancer (NSCLC) patients have been getting longer. However, clinical factors which contributed to the extension of survival periods of these patients remain unclear. We investigated overall survival, prognostic factors and treatments patterns of EGFR m+ NSCLC patients in real-world clinical practice.
Methods:
This is a multi-center, observational, retrospective study. Histologically or cytologically diagnosed EGFR m+ NSCLC patients who were started first-line treatment from 1/1/2008 to 31/12/2012 were enrolled. The primary objective was the estimated OS. The secondary objectives were to determine prognostic factors, real-world treatment patterns.
Results:
1,660 EGFR m+ NSCLC patients were enrolled from 17 hospitals in Japan (median age 67.0 years, female 64.8%, 38.9% had smoking history, ECOG-performance status 0, 1, 2, 3, 4 were 39.5%, 41.1%, 7.1%, 4.9%, 0.7%, respectively, adenocarcinoma 95.2%, 50.1% exon 19 deletion, 66.7% at stage IV). Median estimated OS was 29.7 months. Cox regression analysis revealed age, smoking history, performance status, histological diagnosis, EGFR mutation type and clinical stage were independently associated with OS. Five year survival rate of stage IV patients was 13.8%. The median number of treatment regimens was two. EGFR-TKI and platinum-doublet chemotherapy were most frequently used as first- and second-line treatments.
Conclusion:
Real world treatment of the large data-set of 1,660 EGFR m+ NSCLC patients was retrospectively investigated. Median OS was 29.7 months and EGFR-TKIs are major components of the treatment regimens for these patients in Japan. (NCT0247520)
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P2.03a - Poster Session with Presenters Present (ID 464)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03a-009 - Clinical Outcome of Node-Negative Oligometastatic Non-Small Cell Lung Cancer (ID 4357)
14:30 - 14:30 | Author(s): M. Takeda
- Abstract
Background:
The concept of “oligometastasis” has emerged as a basis on which to identify patients with stage IV non–small cell lung cancer (NSCLC) who might be most amenable to curative treatment. Although such patients without regional lymph node metastases tend to have a longer overall survival (OS) than those with regional lymph node involvement, limited data have been available regarding the survival of patients with node-negative oligometastatic NSCLC. We have therefore now evaluated the clinical outcome of stage IV node-negative oligometastatic NSCLC.
Methods:
Consecutive patients with advanced NSCLC who attended Kindai University Hospital between January 2007 and January 2016 were recruited to this retrospective study. Patients with regional lymph node–negative disease and a limited number of metastatic lesions (≤5) per organ site and a limited number of affected organ sites (1 or 2) were eligible.
Results:
Eighteen patients were identified for analysis during the study period. The most frequent metastatic site was the central nervous system (CNS, 72%). Most patients (83%) received systemic chemotherapy, with only three (17%) undergoing aggressive surgery, for the primary lung tumor. The CNS failure sites for patients with CNS metastases were located outside of the surgery or radiosurgery field. The median OS for all patients was 15.9 months, with that for EGFR mutation–positive patients tending to be longer than that for EGFR mutation–negative patients.
Conclusion:
Our results indicate that a cure is difficult to achieve with current treatment strategies for NSCLC patients with synchronous oligometastases, although a few long-term survivors and a smaller number of patients alive at last follow-up were present among the study cohort. There is an urgent clinical need for prospective evaluation of surgical resection as a treatment for oligometastatic NSCLC negative for driver mutations.
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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-002 - Phase I Study of DS-6051b, a ROS1/NTRK Inhibitor, in Japanese Subjects with Advanced Solid Tumors Harboring Either a ROS1 or NTRK Fusion Gene (ID 4366)
14:30 - 14:30 | Author(s): M. Takeda
- Abstract
Background:
Oncogenic gene fusions of ROS1 or NTRK have been reported in various cancers. DS-6051b is an orally available small molecule receptor tyrosine kinase inhibitor with high affinity for the ROS1 and NTRK receptors. Non-clinical pharmacology studies demonstrated anticancer activity of DS-6051b against several types of human tumor harboring ROS1 or NTRK fusion gene in cultured cells and xenograft models.
Methods:
This is an ongoing phase 1 study in Japanese subjects with advanced solid tumors harboring either a ROS1 or NTRK fusion gene. Subjects receive doses of DS-6051b from 400mg to 800mg once daily (QD). Pharmacokinetics (PK) samples are collected from Day1 to Day22. Primary objective is to assess the safety profile and secondary objectives are to determine the maximum tolerated dose (MTD), the recommended phase 2 dose (RP2D), and to assess the PK profile. The efficacy of DS-6051b is an exploratory assessment performed by investigator judgment per RECIST v.1.1.
Results:
As of June 27, 2016, a total of 9 subjects were enrolled. Median age was 51 (43-69) years, 56% were female, all 9 subjects were ROS1 fusion positive non-small cell lung cancer patients, and 3 subjects had prior crizotinib treatment. Subjects received DS-6051b at doses of 400mg QD (n=6) and 800mg QD (n=3). There were no DLTs in the 400mg QD cohort, and 2 out of 3 subjects in the 800mg QD cohort experienced DLT with grade 3 AST/ALT increased. To evaluate the MTD and RP2D more in detail, 600mg QD cohort is planned. Common adverse events were AST increased, ALT increased, diarrhea, and constipation. Among 7 patients who had target lesion, 4 subjects showed partial response, 3 subjects showed stable disease. PK data indicated the plasma drug concentration increases as the dose increases.
Conclusion:
This study is categorized as “Clinical Trial in Progress”. This study was initiated from February 2016 and estimated primary completion date will be September 2018.
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P3.02a - Poster Session with Presenters Present (ID 470)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02a-005 - The Association between the Percentage of Anaplastic Lymphoma Kinase(ALK)-Positive Cells and Efficacy of ALK Inhibitor (ID 4621)
14:30 - 14:30 | Author(s): M. Takeda
- Abstract
Background:
The purpose of the study was to explore the association between the percentage of ALK+ cells in fluorescent in situ hybridization (FISH) and the clinical efficacy of ALK inhibitor.
Methods:
A total of 73 patients (pts) with ALK rearrangement who were identified the percentages of ALK+ cells in FISH and were treated with ALK inhibitor, were enrolled at three participating institutions. Retrospectively, we evaluated progression-free survival (PFS) by log-rank test and Kaplan–Meier method.
Results:
Median % ALK+ cells in FISH was 54% (range 15-100%). Fifty (68.5％) pts used crizotinib (CRZ) and 23 (31.5%) pts used alectinib (ALC) as the first ALK inhibitor. Among 57 pts who were evaluated by immunohistochemical (IHC) staining, 10 had no detectable expression of the ALK protein and the percentage of ALK+ cells was all within 15-29%. The PFS of pts with 15-29% ALK+ cells was shorter than that with 30% or more ALK+ cells (CRZ group: 1.4 months [95% CI: 0.2-4.2] in 15-19% ALK+ cells, 3.25 months [0.47-Not Estimated (NE)] in 20-29%, 6.77 months [4.27-12.6] in 30-100%, p < .001. ALC group: 6.4 months [3.03-16.8] in 20-29%, 23.1 months [7.8-NE] in 30-100%, p = 0.547). Moreover, among pts with 15-29% ALK+ cells, median PFS of pts with IHC- was significantly shorter than that with IHC+ (CRZ group: 1.3 vs 5.6 months, p = 0.009. ALC group: 0.87 vs 40.3 months, p = 0.004).
Conclusion:
The case in 15-29% ALK+ cells and IHC- could not obtain the benefit of the ALK inhibitor. However, if the case is IHC+, the long PFS could be expected despite the percentage of ALK+ cells in FISH.
