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I. Okamoto
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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): I. Okamoto
- 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-056 - Phase II Trial of Weekly Nab-Paclitaxel for Previously Treated Advanced Non–Small Cell Lung Cancer: KTOSG Trial 1301 (ID 4004)
14:30 - 14:30 | Author(s): I. Okamoto
- Abstract
Background:
We performed an open-label, multicenter, single-arm phase II study (UMIN ID 000010532) to prospectively evaluate the efficacy and safety of nab-paclitaxel for previously treated patients with advanced non–small cell lung cancer (NSCLC).
Methods:
Patients with advanced NSCLC who experienced failure of prior platinum-doublet chemotherapy received weekly nab-paclitaxel (100 mg/m[2]) on days 1, 8, and 15 of a 21-day cycle until disease progression or the development of unacceptable toxicity. The primary end point of the study was objective response rate (ORR).
Results:
Forty-one patients were enrolled between September 2013 and April 2015. The ORR was 31.7 % (90% confidence interval, 19.3% to 44.1%), which met the primary objective of the study. Median progression-free survival was 4.9 months (95% confidence interval, 2.4 to 7.4 months) and median overall survival was 13.0 (95% confidence interval, 8.0 to 18.0 months) months. The median number of treatment cycles was four (range, 1 to 17) over the entire study period, and the median dose intensity was 89.1 mg/m[2] per week. Hematologic toxicities of grade 3 or 4 included neutropenia (19.5%) and leukopenia (17.1%), with no cases of febrile neutropenia being observed. Individual nonhematologic toxicities of grade 3 or higher occurred with a frequency of <5%.
Conclusion:
Weekly nab-paclitaxel was associated with acceptable toxicity and a favorable ORR in previously treated patients with advanced NSCLC. Our results justify the undertaking of a phase III trial comparing nab-paclitaxel with docetaxel in this patient population.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-073 - A Phase II, Liquid Biopsy Study Using Digital PCR in EGFR Mutated, Lung Cancer Patients Treated with Afatinib (WJOG 8114LTR) (ID 4754)
14:30 - 14:30 | Author(s): I. Okamoto
- Abstract
Background:
Liquid biopsy is an ideal strategy to monitor mutation status of cancer repeatedly and less invasively. In chronic myeloid leukemia, early remission of mutated cells was reported as a surrogate of longer efficacy. In epidermal growth factor (EGFR) mutated non-small cell lung cancer (NSCLC), to detect resistant mutation (exon20 T790M) during treatment is clinically important because newer tyrosine kinase inhibitors (TKIs) have been developed. Although some reports have mentioned the utility of liquid biopsy in EGFR mutated NSCLC, most were single-institutional, retrospective studies.
Methods:
West Japan Oncology Group (WJOG) 8114LTR is a multi-institutional, prospective liquid biopsy study in advanced NSCLC. Chemotherapy naïve, advanced NSCLC patients with EGFR-sensitizing mutation will receive afatinib monotherapy (40 mg/body) until progressive disease (PD) or unacceptable toxicity. Plasma DNA will be obtained from patients at baseline, 2, 4, 8, 12, 24, 48 weeks, and at PD. Three types of common EGFR mutations (exon 19 deletion, exon 20 T790M and exon 21 L858R) will be analyzed using plasma DNA with multiplexed, pico-droplet digital PCR assay (RainDrop® system, RainDance Technologies, Billerica, MA). Primary endpoint of this study is the concordance of EGFR mutation status between tissue and plasma at baseline. Secondary endpoints are overall response rate, progression-free survival and safety. This is the first report on the primary endpoint and early remission rate based on mutated cf-DNA. This study was registered at UMIN (ID: 000015847).
Results:
Fifty-seven patients were registered and samples from 55 patients were analyzed. Clinical characteristics were as follows; median age: 69 years, male / female: 25/30, PS 0/1: 23/32, c-stage III / IV / post-operative relapse: 2/37/16, exon 19 deletion / exon 21 L858R: 28/27. Sensitivity of plasma sample was 63.6% among overall, while that was 84.6% in patients with distant metastasis. Eighty-two percent of plasma positive patients at baseline showed molecular response in plasma after two weeks of afatinib treatment. De novo T790M mutation was detected in one patient (2%) from plasma samples.
Conclusion:
Liquid biopsy seemed to be suitable especially in patients with distant metastasis. Early molecular remission (within two weeks) was observed in 70% of patients.
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P3.02b-097 - Experience of Re-Biopsy (Biopsy at Progression) of EGFR Mutant Non-Small Cell Lung Cancer Patients in Japan: A Retrospective Study (ID 4049)
14:30 - 14:30 | Author(s): I. Okamoto
- Abstract
Background:
To confirm mechanisms of resistance to targeted therapy and to evaluate future treatment strategy, biopsy at progression is important and necessary. Since biopsy at progression is not standard of care, we investigated real-world clinical practice in Japanese patients with non-small cell lung cancer (NSCLC) patients harboring the epidermal growth factor receptor (EGFR) gene mutation.
Methods:
This was a retrospective, multi-center, observational study in Japan. EGFR mutation positive NSCLC patients who developed disease progression after treatment by EGFR tyrosine kinase inhibitor were enrolled. The primary objective was the success rate of re-biopsy (biopsy at progression). The secondary objectives were differences of between the first biopsy and re-biopsy (e.g. sampling method, target organ of biopsy) and complications associated with re-biopsy.
Results:
395 patients were evaluated, median age was 63 years, and the most common histological type was adenocarcinoma (96.2%). Success rate of re-biopsy was 79.5% (314/395) of patients. Compared with the first biopsy, surgical biopsy increased from 1.8% to 7.8%, percutaneous tissue biopsy increased from 7.6% to 29.1%. Most commonly performed gene mutation tests using specimen collected by re-biopsy were EGFR (94.3%), EML4-ALK (22.0%) and KRAS (14.3%). T790M mutation was detected in 147 (49.7 %) out of 296 patients. 23 patients (5.8%) had complications associated with re-biopsy, the most common complication was pneumothorax. A repeated re-biopsy was successful in 87.5% (28/32) of patients.Table. Re-biopsy success rate by site and sampling method No. of patients Success rate (%) By Site Primary site 220 168 (76.4%) Metastatic site 121 103 (85.1%) Lymphnodes 50 40 (80.0%) Others 4 3(75.0%) By sampling method Transbronchial biopsy; forceps 204 147(72.1%) Transbronchial biopsy; needle 41 34 (82.9%) Percutaneous needle biopsy under CT guidance 77 66 (85.7%) Percutaneous needle biopsy under ultrasonic guidance 36 34 (94.4%)
Conclusion:
The observed success rate of re-biopsy was approximately 80% in this study. T790M detection rate was comparable to the previously reported studies. Re-biopsy for the EGFR TKI failure NSCLC patients is feasible in Japan.
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P3.02c - Poster Session with Presenters Present (ID 472)
- 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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P3.02c-001 - Phase I Study of Salazosulfapyridine Targeting Cancer Stem Cells in Combination with CDDP and Pemetrexed for Chemo-Naïve Advanced Non-Sq NSCLC (ID 4318)
14:30 - 14:30 | Author(s): I. Okamoto
- Abstract
Background:
Variant splicing isoforms of CD44 (CD44v) are a marker of cancer stem cells (CSCs) in solid tumors. CD44v stabilizes the glutamate-cystine transporter subunit xCT and thereby promotes synthesis of the intracellular antioxidant glutathione and protects CSCs from oxidative stress. Salazosulfapyridine (SASP) is an inhibitor of xCT activity, and, in combination with cisplatin (CDDP), it attenuates the increase in the proportion of CD44v-positive tumor cells during the growth of tumor xenografts in mice.
Methods:
Individuals with advanced (stage IIIB or IV) nonsquamous non–small cell lung cancer are eligible to enroll in a phase I dose-escalation study (standard 3+3 design) of SASP in combination with CDDP and pemetrexed (PEM) as first-line treatment. Patients receive SASP daily as well as CDDP (75 mg/m[2]) and PEM (500 mg/m[2]) on day 1 of a 21-day cycle. The primary end point is the percentage of patients who experience dose-limiting toxicity (DLT) between administration of the first dose of SASP (day 1) and day 21.
Results:
From April 2015 to January 2016, 15 patients were enrolled in the study (mean age, 64 years; age range, 42–74 years; male/female ratio, 10/5; ECOG performance status 0/1 ratio, 6/9). Immunohistochemical staining of tumor biopsy specimens revealed that the proportion of CD44v-positive cells was >10% in 9 patients before SASP treatment. No DLT was observed in the first three patients treated at SASP dose level 1 (500 mg TID) or those treated at dose level 2 (1000 mg TID). At dose level 3 (1500 mg TID), two of three patients experienced a DLT (anorexia of grade 3). We enrolled additional patients at dose level 2 and two of the total of five patients treated at this dose level experienced DLTs (hypotension or pneumonitis, each of grade 3). To confirm the safety of dose level 1, we enrolled additional patients at this dose level and one of the total of six patients treated at this dose level experienced DLTs (AST and ALT elevation, each of grade 3). Exposure of SASP following oral administration varied markedly among individuals according to ABCG2 and NAT2 genotypes as previously reported.
Conclusion:
SASP 500 mg TID was the recommended dose when administered with CDDP plus PEM.
