Virtual Library
Start Your Search
J.S. Ahn
Author of
-
+
MINI 05 - EGFR Mutant Lung Cancer 1 (ID 103)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:Y. Yatabe, R. Perez-Soler
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 2a-3b
-
+
MINI05.06 - A Phase Ib/II Study of Afainib plus Nimotuzumab in Non-Small Cell Lung Cancer Patients with Acquired Resistance to Gefitinib or Erlotinib (ID 667)
17:15 - 17:20 | Author(s): J.S. Ahn
- Abstract
- Presentation
Background:
Afatinib (A) is a potent irreversible EGFR TKI and nimotuzumab (N) is a humanized anti-EGFR mAb. In this phase Ib/II study, we aimed to assess the safety and activity of A plus N in advanced NSCLC patients with acquired resistance to gefitinib or erlotinib.
Methods:
Major inclusion criteria were advanced NSCLC with activating EGFR mutation or disease control for at least six months with previous gefitinib or erlotinib therapy. In the phase Ib study using classic 3+3 dose escalation method, patients were treated with A 40mg/d or 30mg/d in combination with N 100mg/w or 200mg/w. One cycle was composed of 4 weeks of treatment. In the phase II study, patients were treated with A plus N in the level of RP2D defined in the phase Ib study.
Results:
Overall, fifty pts were enrolled and treated: 13 in phase Ib and 37 in phase II. At the starting dose level (A 40mg/d + N 100mg/w), one out of 6 pts experienced end-of-cycle 1 DLT (G3 diarrhea), and the dose was up to the next level of A 40mg/d + N 200mg/w. Out of 6 pts at this level, 2 pts experienced DLTs (G3 diarrhea and G3 neutropenia, respectively), and RP2D was accordingly determined as A 40mg/d + N 100mg/w. In the whole treatment duration of the phase II, there was no treatment related death and 10 pts (20%) experienced any grade 3 adverse event, including diarrhea and skin rash. Out of evaluable 50 pts in the phase Ib/II study, the response rate was 36% (18 achieved partial response out of 50) and the median PFS was 4.4 months (95% CI:3.2-5.5 months).
Conclusion:
A and N showed an acceptable safety profile and promising antitumor activity in advanced NSCLC patients with acquired resistance to gefitinib or erlotinib.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
MINI 26 - Circulating Tumor Markers (ID 148)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:M. Macmanus, C. Aggarwal
- Coordinates: 9/09/2015, 16:45 - 18:15, 205+207
-
+
MINI26.11 - Longitudinal Monitoring of EGFR Mutations in Plasma of EGFR Mutant NSCLC Patients Treated with EGFR TKIs: Korean Lung Cancer Consortium (ID 1130)
17:40 - 17:45 | Author(s): J.S. Ahn
- Abstract
- Presentation
Background:
Detection of epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC) patients is mainly based on tissue biopsy, which is invasive and time consuming. Furthermore, there is still a need for serial monitoring of EGFR mutations and detection of EGFR tyrosine kinase inhibitors (TKIs) resistance. We hypothesized that plasma-based EGFR mutation analysis may be feasible for monitoring response to EGFR TKIs and could be used to predict the resistance.
Methods:
From January 2012 to October 2014, 200 EGFR mutant NSCLC patients were enrolled and treated with EGFR TKIs (141 patients for gefitinib, 46 patients for erlotinib, and 13 patients for afatinib). Plasma samples were prospectively obtained every 2 months from baseline until disease progression. The longitudinally collected plasma samples (n = 368) from 81 patients who progressed were analyzed using droplet digital PCR (ddPCR). We identified an association between serial EGFR mutant titers in plasma cell-free DNA (cfDNA) samples and the patient’s clinical response to EGFR TKIs.
Results:
Of a total 58 baseline cfDNA samples available for ddPCR, 43 (74%) samples demonstrated same mutation in the matched tumors (i.e. sensitivity: 70.8% (17/24) for L858R vs 76.5% (26/34) for exon 19 deletions). The concordance rate of plasma with tissue results of EGFR mutation was 88% for L858R and 86% for exon 19 deletion, respectively. Of the 54 patients with both before and after treatment plasma samples, 40 patients showed a dramatic decrease of mutant copies (greater than 50%) in blood in the first 2 months after treatment. We also found the secondary mutation (T790M) emerged in 28 patients around 3~13 months after treatment and in 4 patients before the treatment. Elevated circulating mutations (L858R/ex19/T790M) can be detected in 5 patients before disease progression as determined by CT scan.
Conclusion:
These results suggest that ddPCR is an appropriate method for determining plasma-based EGFR mutation status and may aid in monitoring response to EGFR TKIs and early detection of EGFR TKIs resistance.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
MINI 30 - New Kinase Targets (ID 157)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:K. Park, M. Villalona
- Coordinates: 9/09/2015, 18:30 - 20:00, Four Seasons Ballroom F3+F4
-
+
MINI30.11 - Efficacy and Safety of Dovitinib in Advanced Squamous Cell Lung Cancer with FGFR1 Amplification: A Single-Arm, Phase II Study (ID 666)
19:30 - 19:35 | Author(s): J.S. Ahn
- Abstract
- Presentation
Background:
FGFR1 amplification is one of the most common potential driving oncogenes in squamous cell carcinoma (SCC), which accounts for 20% of non-small cell lung cancer (NSCLC) squamous cell carcinoma. This phase II study evaluated the efficacy and toxicity profile of dovitinib, an orally active FGFR (fibroblast growth factor receptor) inhibitor, in advanced SCC patients.
Methods:
Patients with histological confirmed advanced squamous cell NSCLC and previously treated with at least one cytotoxic chemotherapy were enrolled from April 2013 to December 2014. All patients had FGFR1 gene amplification more than 5 copies by fluorescent in situ hybridization (FISH). Each 7-day treatment cycle consisted of dovitinib 500mg orally administration on days 1 to 5 and 2 days off. Primary endpoint was overall response rate and secondary endpoints included PFS, OS and toxicity.
Results:
All 26 patients were male with the median age of 68 years (range, 52 – 80). Most patients were ever smokers (96%) and had good ECOG (0-1) performance status (85%). The median number of dovitinib treatment cycles administered was 2.5 (range, 1-12). The overall response rate (ORR) was 11.5% (95% CI, 0.8 – 23.8) and disease control rate (DCR) was 50% (95% CI, 30.8 – 69.2). There were three partial responses (PR) and ten stable diseases (SD). Duration of response in 3 patients who achieved PR was 4.5+, 5.1+ and 6.1months. After the median follow-up duration of 15.7 months (range, 5.8 – 25.6 ), the median overall survival (OS) was 5.0 months (95% Confidential Interval, 3.61 – 6.39) and progression-free survival (PFS) was 2.9 months (95% CI, 1.54 – 4.26). Grade 1/2 fatigue (69%) and anorexia (85%) were most commonly reported adverse events and 12 patients (46%) required dose reduction of dovitinib.
Conclusion:
Dovitinib treatment a showed modest efficacy in advanced squamous cell lung cancer patients with FGFR1 amplification. Further studies to evaluate other biomarkers correlated with the efficacy of dovitinib in SCC should be warranted.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
ORAL 11 - Clinical Trials 1 (ID 100)
- Event: WCLC 2015
- Type: Oral Session
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:A.K. Nowak, F. Detterbeck
- Coordinates: 9/07/2015, 10:45 - 12:15, 702+704+706
-
+
ORAL11.06 - A Prospective Phase II Study of Cisplatin and Cremorphor EL-Free Paclitaxel (Genexol-PM) in Patients with Unresectable Thymic Epithelial Tumors: Can 18F-FDG PET/CT Play a Role? (ID 2221)
11:39 - 11:50 | Author(s): J.S. Ahn
- Abstract
- Presentation
Background:
We conducted a prospective phase II study of cisplatin plus Cremorphor EL-free paclitaxel (Genexol-PM) in patients with unresectable thymic epithelial tumors (TETs) in order to determine the efficacy and tolerability of the combination.
Methods:
Patients were treated with cisplatin (70 mg/m[2]) and Genexol-PM (230 mg/m[2]) every three weeks for a maximum of six cycles. The primary end point of this study was objective response rate (ORR), and secondary end points included toxicity, progression-free survival (PFS), overall survival (OS), correlation between early [18]F-FDG PET/CT response and PFS, and correlation between baseline FDG uptake and histology.
Results:
Forty-two patients with unresectable thymoma (n=14) or thymic carcinoma (n=28) were enrolled. The median age was 59 years (range, 25-77) and 30 (71%) patients were male, and 39 (93%) had an ECOG PS of 1. The median number of treatment cycles was six (range 1-6). For 40 assessable patients, the ORR was 62.5% (95% confidence interval [CI] 47.6-77.4) with rates of 46% (95% CI 23.3-76.9) for advanced thymoma (n=13) and 70% (95% CI 52.0-82.1) for thymic carcinoma (n=27). With a median follow-up of 15.5 months, the median PFS was 9.8 months (11.4 months for thymoma vs. 8.1 months for thymic carcinoma, with median follow-ups of 16.1 vs. 15.5 months, respectively). The two-year OS was 77.9% for thymoma and 65.9% for thymic carcinoma. There were no treatment-related deaths. The most common grade 3 and 4 treatment-related adverse event was neutropenia in 11 patients (26%). Sixteen (38%) patients experienced grade 2 hypersensitivity reactions. There was no correlation between early PET response and PFS, but tumor histology (thymoma vs. thymic carcinoma) was correlated with SUV~max~ before chemotherapy.
Conclusion:
These data suggest that the combination of cisplatin and Genexol-PM is highly effective and tolerable for the treatment of unresectable TETs, especially in patients with thymic carcinoma.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
-
+
P1.08-037 - PD-L1 Expression in Surgically Resected Thymic Epithelial Tumor (ID 1488)
09:30 - 09:30 | Author(s): J.S. Ahn
- Abstract
Background:
Blockade of the immune checkpoint programmed death receptor ligand-1 (PD-L1)/PD-1 pathway has recently shown clinical activity across many tumor types. PD-L1 protein expression by immunohistochemistry (IHC) is emerging as a predictive biomarker of response to these therapies. Hence, we studied PD-L1 expression in a thymic epithelial tumor (TET).
Methods:
Of the patients who previously underwent resection of TET at Samsung Medical Center between January 2000 and January 2013, 220 patients who had available tissue block for immunohistochemistry were included. Formalin-fixed paraffin embedded tumor samples were stained with murine monoclonal antibody (clone h5H1) to human PD-L1. PD-L1 staining was classified based on intensity and moderate or strong intensity in 5% or more of tumor tissues was considered as positive PD-L1 expression.
Results:
The median age was 52 years (range, 18-81), and 57.7% of patients were male. WHO histologic type was mostly B2 (N=96, 43.6%), followed by C (N=48, 21.8%), B3 (N=47, 21.4%) and neuroendocrine tumor (N=17, 7.7%). R0 resection was possible in 193 patients (87.7%). Positive PD-L1 expression was observed in 83 samples (37.7%). PD-L1 expression and histologic type was significantly correlated, with high PD-L1 expression in histologic type B2/B3/C (7.1% vs. 42.4% in type A/AB/neuroendocrine tumor vs. type B2/B3/C; P<0.001). PD-L1 expression did not affect overall survival both in univariate and multivariate survival analysis.
Conclusion:
In TET, PD-L1 expression was positive in 37.7% and it was more frequently observed in aggressive histology (B2/B3/C). PD-1/PD-L1 targeting agents could be a promising therapy for TET.
-
+
P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
-
+
P2.04-004 - The BIM Deletion Polymorphism in Patients with EGFR-Mutant Non-Small Cell Lung Cancer Treated with EGFR Tyrosine Kinase Inhibitors (ID 1126)
09:30 - 09:30 | Author(s): J.S. Ahn
- Abstract
Background:
A germline BIM deletion polymorphism has been proposed to predict poor treatment response to certain kinase inhibitors. The purpose of this study was to explore whether the BIM deletion polymorphism predicts treatment efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in Korean patients with EGFR-mutant NSCLC.
Methods:
Peripheral blood samples from a total of 205 patients with EGFR-mutant NSCLC who were treated with EGFR TKIs between July 2008 and April 2013 were included. The incidence of BIM deletions in these samples was detected by polymerase chain reaction. We compared the clinical outcomes in patients with and without the polymorphism after treatment with EGFR TKIs (gefitinib or erlotinib).
Results:
The BIM deletion polymorphism was present in 15.6% (32/205) of patients. One patient was homozygous for the deletion, and the remaining 31 had heterozygous deletions. The majority of patients were < 65 years old (74%), female (68%), never smokers (76%), and had stage IV NSCLC (67%). There were no associations between the BIM deletion polymorphism and clinicopathological features including gender, age, smoking status, histology, stage, and number of metastasis sites. Patients with and without the BIM deletion polymorphism had similar ORRs (91% vs. 84%, P = 0.585). Progression-free survival (PFS) and overall survival (OS) did not differ significantly between patients with and without the BIM deletion polymorphism (median PFS 12 vs. 11 months, P = 0.160; median OS 31 vs. 30 months, P = 0.452). Multivariate analysis identified significantly predictive markers for clinical outcomes of EGFR TKIs including ECOG PS 0-1, adenocarcinoma histology, recurrent disease, and EGFR mutation type. The results were validated in an independent cohort of 69 NSCLC patients.
Conclusion:
It remains to be determined whether the BIM deletion polymorphism provides intrinsic resistance or decreased sensitivity to EGFR TKIs in EGFR-mutant NSCLC patients.
-
+
P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
-
+
P3.01-016 - Does Sequence of Cranial Radiotherapy Matter in EGFR Mutant Non-Small Cell Lung Cancer Patients with Brain Metastasis? (ID 2260)
09:30 - 09:30 | Author(s): J.S. Ahn
- Abstract
Background:
The incidence of brain metastasis in EGFR mutant advanced non-small cell lung cancer (NSCLC) is higher than EGFR wild type at the time of diagnosis. Although cranial radiotherapy is considered standard treatment for brain metastasis, EGFR tyrosine kinase inhibitors (TKIs) alone have shown promising activity with up to 80% of response in EGFR mutant NSCLC patients with brain metastasis. However, the role of sequential cranial radiotherapy in EGFR mutant NSCLC treated with EGFR TKIs remains to be determined.
Methods:
Advanced NSCLC patients harboring EGFR mutation (exon 19 deletion or L858R) with brain metastasis who were treated with EGFR TKIs were retrospectively reviewed. To investigate the role of cranial radiotherapy, we analyzed the clinical outcomes between patients treated with EGFR TKIs alone and those treated with cranial radiotherapy (WBRT or SRS) followed by EGFR TKIs (combination therapy). The primary end point was overall survival (OS) and secondary end points included intracranial and extracranial progression free survival (PFS).
Results:
A total of 573 patients who identified EGFR mutation and received EGFR TKIs treatment for NSCLC with brain metastasis from Jan 2007 to Dec 2013 at Samsung Medical Center were enrolled for analysis. Of all 573 patients, 121 patients had brain metastasis in initial work up. There were 38 males and 83 female, a median age was 59.5 years (range 30 – 80). All 121 patients were received gefitinib (n=103) or erlotinib (n=18) as EGFR TKI treatment for 1[st] line chemotherapy. 74 patients were treated with combination therapy (34 patients were taken SRS, 28 patients WBRT, 12 patients both), and 47 patients were treated with EGFR TKI alone. In combination therapy group, 32 patients had brain metastasis related symptoms.The median OS was 38.7 months [95% Confidence Interval 35.0 to 42.5] in combination therapy group and 28.6 months [95% CI 24.3 to 32.8] in EGFR TKI alone group (p=0.295). There were no significant differences in intracrainal PFS (18.6 vs 19.7 months, p=0.343) and extracranial PFS (15.7 vs 15.3 months, p=0.574) between two groups.
Conclusion:
In this retrospective analysis, the combination therapy with cranial radiotherapy followed EGFR TKI did not improve OS and intracranial PFS compared with EGFR TKI alone therapy in EGFR mutant NSCLC patients with brain metastases. Further prospective studies are needed to refine the role of sequential cranial radiotherapy in EGFR mutant NSCLC treated with EGFR TKIs.
-
+
P3.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 214)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
-
+
P3.03-001 - Comparison of Adjuvant Therapy Modes Following Resection in Lung Cancer Patients with Clinically (-) but Pathologically (+) N2 Disease (ID 1298)
09:30 - 09:30 | Author(s): J.S. Ahn
- Abstract
Background:
Mediastinal nodal staging is very important before recommending surgical resection in newly diagnosed non-small cell lung cancer patients. Following curative resection for having apparently clinically uninvolved mediastinal node (cN0-1), some proportion of patients, however, turns out to have pathologically involved mediastinal node (pN2). There have been controversies on optimal adjuvant therapy during past 2 decades in this clinical setting. Systemic chemotherapy, either followed by or concurrent with radiation therapy, has remained most important modality. This study is to evaluate clinical outcomes following similar, but different, 3 adjuvant therapy modalities, in all of which included systemic chemotherapy, at authors’ institute.
Methods:
Between 2006 and 2012, authors identified 240 cN0-1/pN2 patients who received adjuvant systemic chemotherapy following curative resection: chemotherapy alone in 85 patients (Group A); chemotherapy concurrent with thoracic radiation therapy (CCRT) in 68 (Group B); and CCRT followed by consolidation chemotherapy in 87 (Group C), respectively. Chemotherapy dose intensity was lower in CCRT setting than in upfront or consolidation chemotherapy settings, while thoracic radiation therapy dose schedule was the same (50 Gy/25 fractions). Clinical outcomes of loco-regional control (LRC), distant-metastasis free survival (DMFS) and overall survival (OS) were compared among Groups.
Results:
Median follow-up duration was 30 (5~93) months. Median age of all patients was 60 years and 149 patients (62.1%) were male. Majority of patients (224 patients, 93.3%) underwent lobectomy, while 16 (6.7%) did pneumonectomy. Adenocarcinoma was most common in 165 patients (68.8%) followed by squamous cell carcinoma in 53 (22.1%), and others in 22 (9.2%). There was no difference among Groups with respects to pretreatment and treatment characteristics except median age (Group A was older: 63 years vs. 58 years vs. 58 years, p=0.022). LRC, DMFS and OS rates at 5 years in all patients were 75.1%, 38.0% and 76.2%, respectively. Though no significant difference in OS at 5 years among Groups (76.8% vs. 68.4% vs. 82.5%, p=0.096), LRC rate at 5 years was significantly improved by addition of thoracic radiation therapy (62.9% vs. 78.9% vs. 82.9%, p=0.011), while DMFS rate at 5 years was significantly improved by delivering full dose chemotherapy (40.6% vs. 19.4% vs. 28.6%, p=0.018).
Conclusion:
Although in retrospective nature having potential selection bias, current observations support that maximal benefit could be achieved by thoracic radiation therapy concurrent with chemotherapy and consolidation full dose chemotherapy with respects to LRC and DMFS. Further prospective clinical trial would be desired.
