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Y. Chen
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-066 - PDL-1 Expression of Tumor Cell, Macrophage, and Immune Cells on Pleural Effusion (ID 9841)
09:30 - 09:30 | Author(s): Y. Chen
- Abstract
Background:
Immune checkpoint inhibitors provide a new treatment strategy for lung cancer. Therefore, microenvironment of tumor and interaction between immune cells and tumor cells become more important. Until now, the most frequently used marker to predict treatment response is immunohistochemical (IHC) stain of tumor PD-L1. However, the microenvironment of malignant pleural effusion is not clear. Weather we could use IHC stain of PD-L1 on cells of pleural effusion to predict treatment response have not been studied, either.
Method:
We retrospective enrolled patients who received malignant pleural effusion drainage and had cell blocks specimens from 2014-2016. IHC stain for PD-L1 was performed for tumor cells, immune cells, and macrophage of all cell block specimens. An experienced pathologist reviewed all the cell block cytology. The intensity of IHC stain was graded into grade 0, 1, 2, and 3. We also collected the clinicopathological characteristics of all patients.
Result:
PD-L1 expression of pleural effusion tumor cells was associated with the PD-L1 expression of pleural effusion macrophage (p=0.003) and immune cells (p<0.001). However, PD-L1 expression of immune cells is not associated with that of macrophages. PD-L1 expression of tumor cells is correlated with gender (p=0.012), smoking status (p=0.032), and ECOG performance status (p=0.017). Finally, PD-L1 expression of immune cells was associated with overall survival of our patients (p=0.004).
Conclusion:
These results suggested that there might be an immune interaction of pleural effusion tumor cells with macrophage/immune cells, and low expression of PDL1 expression of immune cell are associated with poor survival of lung cancer patients with malignant pleural effusion.
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P1.11 - Patient Advocacy (ID 697)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Patient Advocacy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.11-002 - Lung Cancer in Nonagenarian Patients (ID 7981)
09:30 - 09:30 | Author(s): Y. Chen
- Abstract
Background:
More than half lung cancer patients were aged more than 65-year-old. However the information in elderly patients is few, especially in nonagenarian (more than 90 year old).
Method:
We retrospectively collected clinical data of the lung cancer patient aged more than 90 year old between 2010 and 2014 in single medical center in Taiwan. The characteristics, treatment modality, and survival time were analyzed.
Result:
Eighty-three patients were enrolled: 76 patients (91.6%) were non-small cell carcinoma (NSCLC), and 7 patients (8.4%) were small cell carcinoma (SCLC), with the median overall survival (OS) of 30 and 13 weeks, p=0.005. Nine patients were stage I (10.8%), 4 patients were stage II (4.8%), 11 patients were stage III (13.3%), and 59 patients were stage IV (71.7%), with the median OS of 142, 79, 33, and 21 weeks for stage I, II, III, and IV, p<0.001. Better performance status (PS) had longer OS (median OS of 79, 66, 24, 12, and 3 weeks in PS of 0, 1, 2, 3, 4, p<0.001). Patients of simplified comorbidity score (SCS) >9 had shorter OS, but no statistical significance (median OS of 12 and 32 weeks in >9 and ≤ 9 group, p=0.065). For first-line treatment, 61.5% (8 in 13 stage I and II patients) received curative radiotherapy. For stage III patients, 63.6% (7 in 11 patients) received either radiotherapy or chemotherapy alone without concurrent chemo-radiotherapy; in stage IV, 59.3% (35 in 59 patients) received either chemotherapy or targeted therapy. Tumor EGFR mutation status in 30 of 46 stage IV non-squamous NSCLC patients: 55.6% was wild type and L858R was the most frequent. The response patterns in the E19D/L858R/G719X EGFR mutation under EGFR-TKI were 4 partial response, 5 stable disease, 1 progressive disease, and 3 patients were unevaluable (the response rate of 33.3% and the control rate of 75%). In 19 stage IV non-squamous NSCLC patients under EGFR-TKI, the EGFR mutated patients had longer OS than the wild type or unknown status (median OS of 36, 3, 22 weeks in EGFR mutated, wild type, and unknown status, p=0.018).
Conclusion:
Histology, staging, and ECOG PS had statistical significance affecting OS of nonagenarian patients. The lower SCS score patients had insignificant longer OS. The stage IV EGFR mutated non-squamous NSCLC patients under EGFR-TKI had longer OS than wild type or unknown status. Majority of nonagenarian patients could receive first line treatment, and it is important to find out the appropriate treatment for the “fit” patient.
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-027 - Efficacy and Safety of Nivolumab Therapy for Advanced NSCLC in the Expanded Access Named Patient Program in Taiwan (ID 8711)
09:30 - 09:30 | Author(s): Y. Chen
- Abstract
Background:
Nivolumab is current standard of care for patients with pretreated advanced non-small cell lung cancer (NSCLC). The patients’ and physicians’ experience of using nivolumab in real-world clinical practice in Taiwan is unknown. We aimed to evaluate the efficacy and safety of nivolumab therapy in Taiwan.
Method:
We retrospectively reviewed the medical records of the patients with age > 20 years who were diagnosed to have advanced NSCLC and received nivolumab therapy through the Expanded Access Named Patient Program in 2016. Nivolumab 3 mg/kg was administered intravenously every 2 weeks.
Result:
A total of 94 patients were included in this analysis. The median age was 60 years (range, 31-76), and 63.8% of these patients were non-smoker. Most of the patients (75.5%) had adenocarcinoma histology, and 34.0% of the patients harbored an EGFR mutation. The median cycle number of nivolumab therapy was 9 (range, 1-28). The median treatment duration was 4.6 months (95% CI, 3.0-6.6). Nivolumab monotherapy is still ongoing in 16 patients (17.0%) on the date of data cutoff. The objective response rate was 13.8%. The median overall survival was 12.0 months (95% CI, 9.2 to not reached). In univariate analysis, sex, age, smoking history, EGFR mutation, squamous histology, and previous extracranial irradiation therapy were not predictors of prolonged survival. Only ECOG performance status (PS) < 2 before starting nivolumab therapy was a predictor of prolonged survival (HR: 0.32; 95% CI, 0.17-0.59). The most common treatment related adverse events (AEs) included fatigue (34.0%), nausea (17.0%), rash (12.8%), asthenia (8.5%), and pyrexia (5.3%). Grade ≧ 3 AEs developed in 7.4% of the patients. All grades interstitial lung disease developed in 4.3% of the patients. One patient died of grade 5 diarrhea after one dose of nivolumab therapy.
Conclusion:
The efficacy and safety data in Taiwan were in line with previous clinical trial reports. Patients with PS < 2 may have better survival outcome after receiving nivolumab therapy.
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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)
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P3.01-005 - ASTRIS: A Real World Study of Osimertinib Treatment in Patients with EGFR T790M Positive Advanced NSCLC; Interim Analysis (ID 7884)
09:30 - 09:30 | Author(s): Y. Chen
- Abstract
Background:
Osimertinib is a third-generation, CNS active EGFR-TKI that potently and selectively inhibits both EGFR-sensitizing and EGFR T790M resistance mutations in non-small cell lung cancer (NSCLC). We report interim clinical and molecular diagnostic testing results from a predefined interim analysis of the ongoing ASTRIS study (NCT02474355).
Method:
Patients (pts) received osimertinib 80 mg once daily. Eligible pts had advanced NSCLC that had progressed on prior EGFR-TKI therapy and with a T790M mutation determined by local validated molecular test, WHO performance status (PS) 0−2, acceptable organ and bone marrow function and no history of interstitial lung disease or QTc prolongation. Asymptomatic, stable CNS metastases were permitted. The primary efficacy outcome was overall survival; other outcomes included local test methods, specimen type, EGFR mutations identified, investigator-assessed response rate (RR), progression-free survival and time to treatment discontinuation. Safety data are also reported.
Result:
From 18 Sept 2015 to the planned 3 Nov 2016 data cut-off (DCO), 1217 pts received osimertinib 80 mg once-daily across 14 countries with a median age 64 yrs (27–92 yrs), 67% female, 61% White, 37% Asian, 87% WHO PS 0/1, 44% prior chemotherapy, 45% prior radiotherapy. All pts tested positive for T790M; T790M was reported alone in 185 pts (15%). The most common testing methods were PNA-Clamp 317 pts (27%), Qiagen therascreen 254 pts (22%), and Roche cobas 204 pts (17%). Exon 19 deletion was the most common co-occurring mutation with T790M (57%), followed by L858R (27%). Tissue or cytology specimens were used in 720 pts (59%), plasma in 433 pts (36%), and other specimens in 64 pts (5%). At DCO, the median duration of exposure was 3.8 months (<1–13.2 months) with a median follow-up time of 4.1 months (<1−14 months). In pts evaluable for response, the investigator-assessed RR was 64% (569/886; 95% CI 61, 67). Adverse events (AEs) leading to dose modification and treatment discontinuation were reported in 122 pts (10%) and 54 pts (4%), respectively. Serious AEs were reported in 165 pts (14%) and AEs leading to death in 28 pts (2%).
Conclusion:
ASTRIS is the largest reported global study of osimertinib in pts with T790M-positive NSCLC identified by a wide array of molecular testing methods and from various specimen types. Considering this breadth of T790M testing, the clinical activity of osimertinib is like that observed in the clinical trial program and no new safety signals were identified.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-070 - Investigation of Whether HIF-1α Inhibitors Can Increase EGFR-TKI Effect for Non-Small Cell Lung Cancer Cell Lines (ID 9492)
09:30 - 09:30 | Author(s): Y. Chen
- Abstract
Background:
Hypoxia-inducible factor-1α (HIF-1α) plays a crucial role in cancer progression, metastasis and angiogenesis. Activation HIF–1α pathway is also associated with epithelial growth factor receptor (EGFR) pathways. This study was to investigate whether inhibitors of HIF–1α increase the cytotoxicity of EGFR-tyrosine kinase inhibitors (TKI) on non-small cell lung cancer (NSCLC) and its mechanism.
Method:
NSCLC lines, including A549, Hcc827, Hcc827R, H460, PC-9, H23, H1299, C339, H3255, and H1975 were used as in vitro experiments. Western blot was used to observe expression of HIF-1α. MTT assay was used to investigate effects of different drug concentrations. The combination of EGFR-TKI (gefitinib) and HIF-1α inhibitors was used in EGFR wild-type, and EGFR- mutant cell lines. The combination index (CI) was used to determine the effect of drug combination. The mean CI (mCI) values more than 1.05 or less than 0.95 were defined as antagonism or synergism, respectively.
Result:
Western blot showed that HIF-1α expression was relatively high in EGFR- mutant cell lines and relatively low in EGFR wild-type cell lines. Under normoxia, HIF-1α expression increased in Hcc827 and H460 cell lines. Under hypoxia, HIF-1α expression increased in Hcc827R and H1975 cell lines. MTT assay showed that gefitinib was found to be superior to HIF-1α inhibitors in cytotoxicity effect on EGFR-TKI-sensitive NSCLC lines (PC9, Hcc827, C339, H3255). HIF-1α inhibitor was relatively better than gefitinib in cytotoxicity effect on EGFR-TKI-insensitive NSCLC cell lines (A549, H23, H460, H1299, Hcc827R, H1975). Under normoxia or hypoxia, cytotoxicity effect of HIF-1α inhibitor on EGFR-TKI-insensitive NSCLC cell lines (Hcc827R, H1975, A549, H460) was relatively better than gefitinib. Of five cell lines, including A549, Hcc827, Hcc827R, H460 and PC-9, their CI values for Gefitinib/HIF-1α inhibitor were 1.00, 0.925, 1.32, 0.76 and 1.23, respectively under normoxia. Data showed that cytotoxicity effect of HIF-1α inhibitor antagonized with gefitinib in Hcc827R and PC-9 cell lines. However, cytotoxicity effect of HIF-1α inhibitor synergized with gefitinib in the Hcc827, and H460 cell line. Of four cell lines, including A549, Hcc827, Hcc827R, and H460, their CI values for Gefitinib/HIF-1α inhibitor were 1.23, 1.17, 1.02, and 1.08, respectively under hypoxia. In this study, increased expression of HIF-1α in Hcc827 and H460 under normoxia may be related to synergistic cytotoxicity effect of HIF-1α inhibitors and gefitinib.
Conclusion:
HIF-1α inhibitors demonstrated anti-NSCLC activity in vitro and a selectively synergistic effect with gefitinib in EGFR-TKI-insensitive NSCLC cell line (H460). Our study suggested a potential treatment approach using HIF-1α inhibitors plus gefitinib.
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P3.07 - Immunology and Immunotherapy (ID 723)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.07-011 - Investigation of Autologous Tumor-Killing Effect of Effusion-Associated Lymphocytes in Malignant Pleural Effusion of Lung Cancer (ID 9513)
09:30 - 09:30 | Author(s): Y. Chen
- Abstract
Background:
Many lung cancer patients developed malignant pleural effusion during the course of the disease. Previous studies revealed that the effusion associated lymphocytes (EAL) were in dysfunctional state which appeared to be immunosuppressed and unable to kill tumor cells. This study will evaluate the combined effects of IL-2, IL-12, αCD3 antibody (ab), and PD-1 ab on antitumor activity of lymphocytes. The underlying mechanism and relevant immune biomarkers will also be investigated.
Method:
We choose the malignant pleural effusion from lung cancer patients to analyze the association among lymphocytes, cancer cells, and cytokines in order to realize the lymphocyte immunity in the malignant pleural effusion of lung cancer patients. Flow cytometry was used to determined lymphocyte subpopulation. The Proliferation assay was performed to evaluate the effect of medication on lymphocytes. ELISA was used to evaluate cytokine level. Cell-mediated cytotoxicity assay was performed to evaluate the tumor-killing effect of EAL.
Result:
EAL were isolated from 21 malignant pleural effusions. Lymphocyte subpopulation was determied by flow cytometry, and total lymphocytes were composed of 8.9% exhausted T cells (CD3+/CD8+/ PD-1+), and 27.8% PD1+ NK cells. IL-2+αCD3 ab+pembrolizumab has demonstrated the trend toward to enhance the proliferation of EAL. IL-2+αCD3 ab or IL-2+IL-12+αCD3 ab or IL-2+IL-12+αCD3 ab+pembrolizumab demonstrated the trend for EAL to produce more IFN-γ. IL-2+αCD3 ab or IL-2+IL-12+αCD3 ab demonstred the trend for EAL to produce more IL-10. IL-2+αCD3+pembrolizumab did not demonstrated the trend for EAL to produce more IL-10. The addition of IL-2+αCD3 ab or IL-2+pembrolizumab showed the trend toward increased EAL cytolytic activity against autologous tumors (effector:target cells= 30:1). The addition of IL-2+αCD3 ab did not show the trend toward increased EAL cytolytic activity against autologous tumors in different conditions (effector:target cells= 10:1). The addition of IL-2+αCD3 ab or IL-12+αCD3 ab or IL-2+IL-12+αCD3 ab showed the trend toward increased EAL cytolytic activity against autologous tumors (effector:target cells= 3:1).
Conclusion:
The depressed cellular function of EAL may be potentially reversed with multiple signal stimulation, including IL-2 plus αCD3 ab, IL-2 plus pembrolizumab, IL-12 plus αCD3 ab or IL-2 plus IL-12 and αCD3 ab. Further studies are warranted in order to confirm the synergistic cytotoxicity effect of cytokines plus PD-1 inhibitors.
