Virtual Library
Start Your Search
K. Kishi
Author of
-
+
P1.03 - Chemotherapy/Targeted Therapy (ID 689)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P1.03-031 - Adherence and Feasibility of 2 Treatment Schedules of S-1 as Adjuvant Chemotherapy in Completely Resected Lung Cancer (ID 8829)
09:30 - 09:30 | Author(s): K. Kishi
- Abstract
Background:
S-1 is one of the key-drugs as chemotherapy for the non-small cell lung cancer (NSCLC). We conducted a multicenter randomized study of adjuvant S-1 administration schedules for surgically treated pathological stage IB-IIIA NSCLC patients.
Method:
Patients receiving curative surgical resection were centrally randomized to arm A (4 weeks of oral S-1 and a 2-week rest over 12 months) or arm B (2 weeks of S-1 and a 1-week rest over 12 months). The primary endpoints were total days of administration, and the secondary endpoints were relative total administration dose (relative dose intensity), toxicity, and 3-year disease-free survival. Total days of administration were evaluated according to the cumulative rates of total S-1 administration days within 224 days, at the end of 12 months. Relative dose intensity was defined as (the actual total dose administered divided by the planned total administered dose) × 100.
Result:
From April 2005 to January 2012, 80 patients were enrolled, of whom 78 patients were eligible and assessable. The cumulative rates of total S-1 administration days at the end of 12 months, were 81.3% for arm A (38 cases) and 60.2% for arm B patients (40 cases, p = 0.04). The relative dose intensity was 77.2% for arm A and 58.4% for arm B (p = 0.01). Drug-related grade 3 adverse events were recorded for 11% of arm A and 5% of arm B (p = 0.43). The 3-year disease-free survival rate was 79.0% for arm A and 79.3% for arm B (p = 0.94). Toxicity showed no significant difference among the shorter schedule and the conventional schedule, except for grade 1-3 elevation of bilirubin.
Conclusion:
The superiority of feasibility of the shorter schedule was not recognized in the present study. The conventional schedule showed higher cumulative rates of total S-1 administration days at the end of 12 months (p = 0.04) and relative dose intensity of S-1 (p = 0.01).
-
+
P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P3.01-055 - The Usefulness of Liquid Biopsy for ctDNA in Patients with EGFR-Mutant NSCLC During and After Treatment with EGFR-TKIs (ID 9811)
09:30 - 09:30 | Author(s): K. Kishi
- Abstract
Background:
Non-small-cell lung cancer (NSCLC) patients with activating mutation of epidermal growth factor receptor (EGFR) gene inevitably develop disease progression to EGFR-tyrosine kinase inhibitors (TKIs). T790M gatekeeper mutation accounts for approximately 60% of the acquired resistance, and osimertinib, third generation EGFR-TKI, is effective against such tumors. Demonstration of T790M requires second biopsy, which is inconvenient and sometimes hazardous. Liquid biopsy of circulating tumor DNA (ctDNA) in the plasma is a non-invasive alternative, but clinical relevance of this method is yet to be fully elucidated.
Method:
NSCLC patients with EGFR mutation undergoing 1st- or 2nd-generation EGFR-TKI treatment are monthly or bi-monthly monitored for plasma ctDNA EGFR mutations, including T790M, by Cobas EGFR mutation test® via 10 ml blood sampling. The treatment could be changed on the attending physicians’ discretion, including osimertinib in patients with documented T790M mutation, with continuation of the monitoring. The primary endpoints are T790M positivity rate of ctDNA among patients with tissue-confirmed T790M mutation, and T790M positivity rate of ctDNA at landmark points, such as radiological progression, clinical deterioration or second biopsy of the tumor. The secondary endpoints include EGFR mutation detection rate of plasma ctDNA at landmark points, the interval of tissue and plasma T790M detections, and response rate and progression-free survival in patients treated with osimertinib according to plasma/tissue T790M status.
Result:
From Oct 2016 to Mar 2017, 121 eligible patients were enrolled. The median age 73 years (range, 42-92), 42 male (34.7%), PS 0, 1 and 2 were 64 (52.9%), 54 (44.6%) and 3 (2.5%) respectively. EGFR mutation types were 61 patients (50.4%) del 19, 55 (45.5%) L858R and 5 (4.0%) others. 80 (66.1%) were never smokers. At the time of EGFR-TKI initiation, 82 (67.8%) had advanced and 39 (32.2%) had recurrent diseases. 65 (53.7%) had any prior therapy, including 21 (14.8%) with prior cytotoxic chemotherapy. Used EGFR-TKIs were gefitinib 50 (41.3%), erlotinib 40 (33.1%), and afatinib 31 (25.6%). Newly-diagnosed/on TKI therapy at enrollment was 18 (14.9%)/103 (85.1%). The median follow-up is 12[鈴木1] months. So far, plasma T790M was detected in 8 patients.
Conclusion:
This observational study will elucidate the clinical usefulness and limitations of monitoring of ctDNA for T790M mutation in the real-world setting.
-
+
P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 2
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P3.02-033 - Pathological and Molecular Alterations after First and Second Generation EGFR-TKI Therapy in Patients with EGFR-Mutated Lung Adenocarcinomas (ID 8531)
09:30 - 09:30 | Author(s): K. Kishi
- Abstract
Background:
Molecular alterations, including EGFR T790M point mutation and MET gene amplification, are reported as resistance mechanisms to first and second-generation EGFR tyrosine kinase inhibitors (TKIs). However, pathological transformation after EGFR-TKI administration has not been adequately studied. We compared the pathological alterations before and after EGFR-TKI administration in patients with EGFR-mutated lung adenocarcinomas.
Method:
Between January 2016 and March 2017, 61 patients received first and second generation TKI therapy for EGFR-mutation–positive lung adenocarcinomas or adenosquamous carcinomas. Among them, 31 patients experienced recurrence, and 22 of these patients, for whom diagnosis was confirmed through re-biopsy, were included in this study. Pathological and molecular alterations in the re-biopsy specimens were analyzed for these patients. Based on the 2015 WHO classification, lepidic predominant lung adenocarcinomas were categorized as low grade, papillary or acinar lung adenocarcinoma as intermediate grade, and micropapillary or solid lung adenocarcinoma as high grade.
Result:
The EGFR T790M mutation was positive in 11 of the 22 patients. Seven patients were cytologically diagnosed by pleural and cerebrospinal fluid analysis, as well as by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA). The remaining 15 patients underwent pathologically analysis. Twelve patients were found to have adenocarcinomas, two had large-cell neuroendocrine carcinomas (LCNECs), and one displayed epithelial-mesenchymal transition (EMT). Of the 12 adenocarcinomas analyzed, eight were the same tumor grade before and after TKI therapy, and four were higher grade than before TKI therapy.Figure 1
Conclusion:
Neuroendocrine and epithelial-mesenchymal transformations have an important role in EGFR-TKI resistance mechanisms, as previous reports have shown. Regarding the re-biopsy specimens, in one third of cases, the adenocarcinomas were of a higher tumor grade than the specimens analyzed before EGFR-TKI therapy.
-
+
P3.02-048 - Clinicopathologic Characteristics of Non-Small Cell Lung Carcinomas Habouring MET Exon 14 Skipping Mutations (ID 9667)
09:30 - 09:30 | Author(s): K. Kishi
- Abstract
Background:
Non–small cell lung carcinomas (NSCLC) harboring mutations involving MET exon 14 splice sites may respond to MET inhibitors. We investigated the clinicopathologic characteristics of patients with NSCLC with MET exon 14 skipping mutations.
Method:
We examined 192 patients with NSCLC with wild-type EGFR/KRAS/ALK by reverse transcritase-polymerase chain reaction combined with SYBR Green melting curve/fragment analyses to detect the presence of MET exon 14 mutation. Clinical characteristics of MET exon 14 mutated NSCLC were compared with those of NSCLC with EGFR or KRAS mutations. MET immunohistochemistry and fluorescent in situ hybridization will be performed afterwards.
Result:
MET exon 14 mutations were identified in 21 of 192 NSCLC with wild-type EGFR/KRAS/ALK (10.9%), accounting 6.6% of all NSCLC (n=319). Patients with MET exon 14–mutated NSCLC were significantly older (median age, 77 years) than patients without MET exon 14 mutation (median, 71.5 years), and 12 (57%) were men. MET exon 14-mutated NSCLC were staged as stage 0 (n=1), stage IA (n=12), stage IB (n=4), stage IIA (n=3), or stage IV (n=1). MET exon 14–mutated NSCLC were histologically adenocarcinomas (n=20), consisting of adenocarcinoma in situ (n=1), minimally invasive adenocarcinomas (n=2), invasive adenocarcinomas (n=17) including lepidic (n=7), papillary (n=7), acinar (n=5), or solid (n=1) predominant subtypes, and adenosquamous carcinoma (n=1).
Conclusion:
MET exon 14 mutations were identified in 6.6% of all NSCLC, which may represent a clinically unique molecular subtype and an important therapeutic target in NSCLC.
