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153P: Real-time PCR and digital PCR approach for detecting EGFR status in plasma of patients with NSCLC
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Journal of Thoracic Oncology Vol. 11, Suppl. 4S (2016) S113–S142
(EGFR) mutation-positive non-small cell lung cancer (NSCLC) patients pretreated with EGFR tyrosine kinase inhibitors (TKIs). Methods: We searched the medical records of NSCLC patients who participated in lung cancer clinical trials and underwent mandatory RBs exclusively for the trials from 2012 to 2014 in one Asian medical center. Only patients with EGFR mutation-positive NSCLC who had undergone at least one EGFR TKI therapy before RBs were enrolled. The clinical outcomes were reviewed. Results: We identified 140 patients from 11 clinical trials. Most patients (97.9%) had adenocarcinoma histology, and 73 (52.1%) and 59 (42.1%) patients had deletions in exon 19 and exon 21 L858R mutation, respectively. Before RBs, 108 (77.1%), 83 (59.3%), and 36 (25.7%) patients had been treated with gefitinib, erlotinib, and afatinib, respectively. Most patients (54.3%) discontinued EGFR-TKI therapy less than 30 days before RBs. Sixteen patients (11.4%) underwent multiple RBs for a clinical trial to obtain adequate tissue samples, and 7 patients (5.0%) underwent multiple RBs for different clinical trials. A total of 181 RBs were performed (including 13 paired RBs before and after study treatment), and computed tomographyguided RBs were the most frequently used modality (50.8%), followed by ultrasound-guided (32.0%) and bronchoscopy RBs (16.0%). The most common sites of RBs were lung (69.9%), pleura (8.8%), and liver (6.1%). Pathologic exams disclosed malignant cells in most specimens of RBs (72.9%). Complications of RBs included pneumothorax (10.5%), bleeding (6.1%), and infection (1.1%). Only one patient required chest tube placement for pneumothorax, and two patients underwent endotracheal intubation because of RBs related bleeding. Conclusions: RBs in patients with EGFR mutation-positive NSCLC pretreated with EGFR-TKIs were safe, but potential risk of RBs related complications should be discussed with the clinical trial participants. Legal entity responsible for the study: N/A Funding: N/A Disclosure: C.-C. Ho: Grants from AstraZeneca. J.-Y. Shih: Consultant of Eli-Lilly, Roche, AstraZeneca, Boehringer Ingelheim, Pfizer. C.-J. Yu: Consultant of Roche and Novartis. J. Yang: Consultant and received honoraria from AstraZeneca, Roche/Genentech, Boehringer Ingelheim, MSD, Merck Serono, Novartis, Pfizer, Clovis Oncology, Eli Lilly, Bayer, Celgene, Astellas, Innopharma, Ono Pharmaceutical, and Chugai pharmaceutical. All other authors have declared no conflicts of interest.
that were electively profiled with tumor somatic capture-based NGS between November, 2011 and October, 2015 at the Davidoff Cancer Center, Rabin Medical Center, Israel. Demographic data, clinico-pathologic characteristics and treatment outcomes were collected. Results: 101 sequential advanced lung cancer patients who performed capture-based NGS (median age – 63 years, 53% females, 45% never smokers, 85% adenocarcinoma) were included. NGS was performed upfront or following previous negative/non-conclusive EGFR/ALK testing in 15% and 85% of patients, respectively. 50% of patients performed NGS before 1st line therapy and 50% after treatment failure. One or more actionable genomic alterations were found by NGS in 83% of the patients, with most common genes affected being KRAS (15.1%), EGFR (13.7%), STK11 (6.2%), ALK (5.5%), RET (5.5%), ERBB2 (4.8%) and MET (4.8%). Seventeen patients were diagnosed with an EGFR/ALK aberration after previous negative/false approved standard molecular testing. NGS testing resulted in a change in treatment strategy in 42 patients (42%). With targeted treatment based on the NGS results, overall response rate was 64.3% (complete response rate – 23.8%, partial response rate – 40.5%, stable disease – 9.5%). Survival analysis is not matured yet. Conclusions: This study indicates that NGS is crucial in lung adenocarcinoma with a decision change in almost half of the patients in spite of previous molecular testing. It also reassures the > 60% response rate for targeted therapies in lung cancer, which will probably translate into a survival benefit in the future. Clinical trial identification: This study was approved by the ethical committee of Rabin Medical Center (approval no. 0391–14 RMC). Legal entity responsible for the study: Rabin Medical Center (Clalit) Funding: Rabin Medical Center (Clalit) Disclosure: E. Dudnik: Consultant for BI, Merck/MSD, Roche Pharmaceuticals, Astra Zeneca and received payments upon expenses. A. Dvir, L. Soussan-Gutman: Employee of Teva Pharmaceutical Industries Ltd. N. Peled: Consultant for Pfizer, BI, Roche, AZ, MSD, BMS, Lilly, Novartis and NovellusDx. All other authors have declared no conflicts of interest.
152P The clinical utility of next-generation sequencing in lung cancer A. Belilovski Rozenblum1 , M. Ilouze1 , E. Dudnik1 , D. Flex1 , A. Dvir2 , L. Soussan-Gutman2 , N. Peled1 . 1 Thoracic Cancer Unit, Rabin Medical Center Davidoff Cancer Centre, Beilinson Campus, Petach Tikva, Israel , 2 Oncotest, Teva Pharmaceutical Industries Ltd., Shoam, Israel Background: Targeted therapy significantly prolongs survival in adenocarcinoma of the lung. The current diagnostic practice includes EGFR and ALK testing, while other driver mutations may exist and their blockade may be beneficial as well. Next-Generation Sequencing (NGS) can accurately reveal more actionable genomic alterations than standard diagnostic methods, when performed either upfront, in reflex to initial diagnostic negative results or at treatment failure. However, limited data exists regarding the true influence of these tests on clinical decisions in lung cancer. Methods: This retrospective study includes 101 sequential stage IV lung cancer patients (predominantly adenocarcinoma),
153P Real-time PCR and digital PCR approach for detecting EGFR status in plasma of patients with NSCLC M. Gordiev1 , D. Sakaeva2 , M. Blokhina2 , A. Nikitin3 . 1 Moleculardiagnostic laboratory, Kazan Cancer Centre, Kazan, Russian Federation, 2 Chemotherapy, Republican Clinical Oncology Center, Ufa, Russian Federation, 3 Genetic laboratory, Federal Research and Clinical Center, FMBA, Moscow, Russian Federation Background: The aim of this study was to compare mutation status in FFPE tissue and plasma samples and the evaluation diagnostic characteristics of real-time wild-type blocking PCR (LNA-clamp) assay and digital PCR approach (dPCR). Methods: The study included 89 patients with advanced NSCLC with known tissue mutation status. L858R, del19 and T790M mutations was determined in corresponding blood plasma samples. Isolation and analysis of mutations of EGFR (L858R, deletions of the gene EGFR) from tissue was performed by Qiagen FFPE DNA kit (Germany). For dPCR detection of mutations L858R, T790M and del19 in plasma we used a mixture of probes and primers at final concentrations of 900 and 600 nM, respectively. We used different concentrations plasmid positive controls (0%, 0.5% and 5%). The PCR mixture was prepared by 3D Digital PCR Master Mix according to the manufacturer’s instructions. The detection was carried out using the system
April 2016 QuantStudio® 3D Digital PCR System (ABI, USA). For realtime PCR was used a thermal cycler Rotor-Gene 6000 (Qiagen, Germany), PCR was performed in a final volume of 20 ml, reaction mixture contained 70 mM Tris-HCl (pH 8.8), 16.6 mM ammonium sulphate, 0.01% Tween-20, 2 mM magnesium chloride, 200 nM of each dNTP, 500 nM of primers, 250 nM of fluorescent probe, 1000 nM of blocking probe, 1.5 units Taq-DNA polymerase. Probes used in fluorescent dyes – FAM and VIC, quenchers – BHQ-1 and BHQ-2. Sets of oligonucleotides were designed and produced by “Testgen Ltd” (Russia). Results: By comparing of the EGFR mutations status in plasma and tumor samples concordance was 88.7% [95% CI 85%, 92%], sensitivity – 83.3% [95% CI 76%, 90%], specificity – 100%, PPV – 100%. The analytical sensitivity of dPCR was 0.1% Analytical specificity – 99.5%. Analytical sensitivity for real-time PCR was 0.2%, the analytical specificity – 99.7%. Conclusions: Digital PCR has demonstrated the best analytical sensitivity, wherein concordance with real-time PCR was 100%. Legal entity responsible for the study: Kazan Clinical Oncology Center, Kazan, RU Funding: Kazan Clinical Oncology Center, Kazan, RU Disclosure: All authors have declared no conflicts of interest. 154P Plasma dynamic monitoring of soluble c-Met level for EGFR-TKI treatment in advanced non-small cell lung cancer H.-F. Gao, Y.-L. Wu, J.-J. Yang, X.-C. Zhang. Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangzhou, China Background: The activation of c-Met has been associated with both primary and acquired resistance to EGFR-TKI therapy in NSCLC patients. It suggested c-Met status during EGFR-TKI therapy should be concerned. Methods: We retrospectively investigated the dynamic change of soluble c-Met level in plasma and the relationship with the clinical outcomes of EGFR-TKI therapy in advanced NSCLC patients. Immunohistochemistry (IHC) was used to assess the expression of c-Met in the resistant tissue. Plasma c-Met levels were assayed in duplicate using a human soluble c-Met quantitative enzymelinked immunosorbent assay (ELISA) kit. Results: A total of 49 advanced NSCLC patients with EGFR-TKI resistance were selected for the present study. When PD, IHC results showed 37(75.5%) of the patients were tissue c-Met negative, 12 (24.5%) were tissue c-Met positive. There was statistically significant difference in dynamic change of soluble c-Met between tissue c-Met negative group and c-Met positive group (P = 0.002). Patients with baseline soluble c-Met levels > 766 ng/ml showed an inferior median PFS (10.2 vs. 14.0 months, P = 0.003) after EGFR-TKI. Multivariate Cox proportional hazards model analyses demonstrated soluble c-Met level was the independent prognostic factor for PFS after EGFR-TKI (P = 0.009, HR 3.583, 95% CI, 1.379–9.312). Conclusions: uble c-Met in plasma by ELISA provided a noninvasive and sensitive assay to predict EGFR-TKI prognosis. Legal entity responsible for the study: Guangdong Lung Cancer Institute Funding: N/A Disclosure: All authors have declared no conflicts of interest.
Abstracts, ELCC 2016 – Advanced NSCLC
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155P PD-L1 polymorphism can predict clinical outcomes of non-small cell lung cancer patients treated with first-line paclitaxel–cisplatin chemotherapy S.K. Do1 , S.Y. Lee2 , J.E. Choi3 , M.J. Hong3 , J.H. Lee4 , J.Y. Park2 . 1 Department of Biochemistry and Cell biology, Kyungpook National University, Daegu, Republic of Korea , 2 Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea, 3 Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea, 4 Departments of Biochemistry and Cell Biology, Kyungpook National University School of Medicine, Daegu, Republic of Korea Background: This study was conducted to investigate whether polymorphisms of genes involved in immune checkpoints can predict the clinical outcomes of patients with advanced stage non-small cell lung cancer (NSCLC) after 1st line paclitaxelcisplatin chemotherapy. Methods: A total of 379 NSCLC patients were enrolled. Twelve single nucleotide polymorphisms (SNPs) of PD-1, PD-L1, and CTLA-4 genes were selected and genotyped. The associations of SNPs with chemotherapy response and overall survival (OS) were analyzed. Results: Among the 12 SNPs investigated, PD-L1 rs2297136T> C and rs4143815C> G were significantly associated with clinical outcomes after chemotherapy. The rs2297136T> C was significantly associated with both better chemotherapy response and better OS, and the rs4143815C> G had a significantly better response to chemotherapy. Consistent with the individual genotype analyses, rs2297136C-rs4143815G haplotype (ht4) carrying variant alleles at both loci was significantly associated with better chemotherapy response and OS compared with combined other haplotypes. Patients with at least one ht4 had significantly better chemotherapy response and OS compared to those without ht4. Conclusions: PD-L1 rs2297136T> C and rs4143815C> G polymorphisms may be useful for the prediction of clinical outcome of 1st line paclitaxel-cisplatin chemotherapy in NSCLC. Further studies are needed to confirm our findings and to understand the role of PD-L1 in the chemotherapy outcome of NSCLC patients. Legal entity responsible for the study: Kyungpook National University Funding: Ministry of Health & Welfare Disclosure: All authors have declared no conflicts of interest. 156P Correlation of baseline value of folate receptor-positive circulating tumor cells and efficacy of pemetrexed and dynamic monitoring study in NSCLC patients receiving first-line platinum-based chemotherapy X. Chen1 , C. Zhou2 , X. Li3 , G. Yang4 . 1 Medical Oncology and Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China , 2 Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China, 3 Dept. of Lung Cancer Immunology, Shangai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China, 4 Research Department, Genosaber Biotec Co. Ltd, Shanghai, China Background: The efficacy of pemetrexed associates with the expression of folate enzymes, however, few serological marker is available to predict its efficacy. Moreover, dynamic monitoring of CTC count can predict the outcome of tumor therapy and the overall survival of the patient. By quantitative determination of folate receptor-positive CTCs, this study investigated the
Journal of Thoracic Oncology Vol. 11, Suppl. 4S (2016) S113–S142
(EGFR) mutation-positive non-small cell lung cancer (NSCLC) patients pretreated with EGFR tyrosine kinase inhibitors (TKIs). Methods: We searched the medical records of NSCLC patients who participated in lung cancer clinical trials and underwent mandatory RBs exclusively for the trials from 2012 to 2014 in one Asian medical center. Only patients with EGFR mutation-positive NSCLC who had undergone at least one EGFR TKI therapy before RBs were enrolled. The clinical outcomes were reviewed. Results: We identified 140 patients from 11 clinical trials. Most patients (97.9%) had adenocarcinoma histology, and 73 (52.1%) and 59 (42.1%) patients had deletions in exon 19 and exon 21 L858R mutation, respectively. Before RBs, 108 (77.1%), 83 (59.3%), and 36 (25.7%) patients had been treated with gefitinib, erlotinib, and afatinib, respectively. Most patients (54.3%) discontinued EGFR-TKI therapy less than 30 days before RBs. Sixteen patients (11.4%) underwent multiple RBs for a clinical trial to obtain adequate tissue samples, and 7 patients (5.0%) underwent multiple RBs for different clinical trials. A total of 181 RBs were performed (including 13 paired RBs before and after study treatment), and computed tomographyguided RBs were the most frequently used modality (50.8%), followed by ultrasound-guided (32.0%) and bronchoscopy RBs (16.0%). The most common sites of RBs were lung (69.9%), pleura (8.8%), and liver (6.1%). Pathologic exams disclosed malignant cells in most specimens of RBs (72.9%). Complications of RBs included pneumothorax (10.5%), bleeding (6.1%), and infection (1.1%). Only one patient required chest tube placement for pneumothorax, and two patients underwent endotracheal intubation because of RBs related bleeding. Conclusions: RBs in patients with EGFR mutation-positive NSCLC pretreated with EGFR-TKIs were safe, but potential risk of RBs related complications should be discussed with the clinical trial participants. Legal entity responsible for the study: N/A Funding: N/A Disclosure: C.-C. Ho: Grants from AstraZeneca. J.-Y. Shih: Consultant of Eli-Lilly, Roche, AstraZeneca, Boehringer Ingelheim, Pfizer. C.-J. Yu: Consultant of Roche and Novartis. J. Yang: Consultant and received honoraria from AstraZeneca, Roche/Genentech, Boehringer Ingelheim, MSD, Merck Serono, Novartis, Pfizer, Clovis Oncology, Eli Lilly, Bayer, Celgene, Astellas, Innopharma, Ono Pharmaceutical, and Chugai pharmaceutical. All other authors have declared no conflicts of interest.
that were electively profiled with tumor somatic capture-based NGS between November, 2011 and October, 2015 at the Davidoff Cancer Center, Rabin Medical Center, Israel. Demographic data, clinico-pathologic characteristics and treatment outcomes were collected. Results: 101 sequential advanced lung cancer patients who performed capture-based NGS (median age – 63 years, 53% females, 45% never smokers, 85% adenocarcinoma) were included. NGS was performed upfront or following previous negative/non-conclusive EGFR/ALK testing in 15% and 85% of patients, respectively. 50% of patients performed NGS before 1st line therapy and 50% after treatment failure. One or more actionable genomic alterations were found by NGS in 83% of the patients, with most common genes affected being KRAS (15.1%), EGFR (13.7%), STK11 (6.2%), ALK (5.5%), RET (5.5%), ERBB2 (4.8%) and MET (4.8%). Seventeen patients were diagnosed with an EGFR/ALK aberration after previous negative/false approved standard molecular testing. NGS testing resulted in a change in treatment strategy in 42 patients (42%). With targeted treatment based on the NGS results, overall response rate was 64.3% (complete response rate – 23.8%, partial response rate – 40.5%, stable disease – 9.5%). Survival analysis is not matured yet. Conclusions: This study indicates that NGS is crucial in lung adenocarcinoma with a decision change in almost half of the patients in spite of previous molecular testing. It also reassures the > 60% response rate for targeted therapies in lung cancer, which will probably translate into a survival benefit in the future. Clinical trial identification: This study was approved by the ethical committee of Rabin Medical Center (approval no. 0391–14 RMC). Legal entity responsible for the study: Rabin Medical Center (Clalit) Funding: Rabin Medical Center (Clalit) Disclosure: E. Dudnik: Consultant for BI, Merck/MSD, Roche Pharmaceuticals, Astra Zeneca and received payments upon expenses. A. Dvir, L. Soussan-Gutman: Employee of Teva Pharmaceutical Industries Ltd. N. Peled: Consultant for Pfizer, BI, Roche, AZ, MSD, BMS, Lilly, Novartis and NovellusDx. All other authors have declared no conflicts of interest.
152P The clinical utility of next-generation sequencing in lung cancer A. Belilovski Rozenblum1 , M. Ilouze1 , E. Dudnik1 , D. Flex1 , A. Dvir2 , L. Soussan-Gutman2 , N. Peled1 . 1 Thoracic Cancer Unit, Rabin Medical Center Davidoff Cancer Centre, Beilinson Campus, Petach Tikva, Israel , 2 Oncotest, Teva Pharmaceutical Industries Ltd., Shoam, Israel Background: Targeted therapy significantly prolongs survival in adenocarcinoma of the lung. The current diagnostic practice includes EGFR and ALK testing, while other driver mutations may exist and their blockade may be beneficial as well. Next-Generation Sequencing (NGS) can accurately reveal more actionable genomic alterations than standard diagnostic methods, when performed either upfront, in reflex to initial diagnostic negative results or at treatment failure. However, limited data exists regarding the true influence of these tests on clinical decisions in lung cancer. Methods: This retrospective study includes 101 sequential stage IV lung cancer patients (predominantly adenocarcinoma),
153P Real-time PCR and digital PCR approach for detecting EGFR status in plasma of patients with NSCLC M. Gordiev1 , D. Sakaeva2 , M. Blokhina2 , A. Nikitin3 . 1 Moleculardiagnostic laboratory, Kazan Cancer Centre, Kazan, Russian Federation, 2 Chemotherapy, Republican Clinical Oncology Center, Ufa, Russian Federation, 3 Genetic laboratory, Federal Research and Clinical Center, FMBA, Moscow, Russian Federation Background: The aim of this study was to compare mutation status in FFPE tissue and plasma samples and the evaluation diagnostic characteristics of real-time wild-type blocking PCR (LNA-clamp) assay and digital PCR approach (dPCR). Methods: The study included 89 patients with advanced NSCLC with known tissue mutation status. L858R, del19 and T790M mutations was determined in corresponding blood plasma samples. Isolation and analysis of mutations of EGFR (L858R, deletions of the gene EGFR) from tissue was performed by Qiagen FFPE DNA kit (Germany). For dPCR detection of mutations L858R, T790M and del19 in plasma we used a mixture of probes and primers at final concentrations of 900 and 600 nM, respectively. We used different concentrations plasmid positive controls (0%, 0.5% and 5%). The PCR mixture was prepared by 3D Digital PCR Master Mix according to the manufacturer’s instructions. The detection was carried out using the system
April 2016 QuantStudio® 3D Digital PCR System (ABI, USA). For realtime PCR was used a thermal cycler Rotor-Gene 6000 (Qiagen, Germany), PCR was performed in a final volume of 20 ml, reaction mixture contained 70 mM Tris-HCl (pH 8.8), 16.6 mM ammonium sulphate, 0.01% Tween-20, 2 mM magnesium chloride, 200 nM of each dNTP, 500 nM of primers, 250 nM of fluorescent probe, 1000 nM of blocking probe, 1.5 units Taq-DNA polymerase. Probes used in fluorescent dyes – FAM and VIC, quenchers – BHQ-1 and BHQ-2. Sets of oligonucleotides were designed and produced by “Testgen Ltd” (Russia). Results: By comparing of the EGFR mutations status in plasma and tumor samples concordance was 88.7% [95% CI 85%, 92%], sensitivity – 83.3% [95% CI 76%, 90%], specificity – 100%, PPV – 100%. The analytical sensitivity of dPCR was 0.1% Analytical specificity – 99.5%. Analytical sensitivity for real-time PCR was 0.2%, the analytical specificity – 99.7%. Conclusions: Digital PCR has demonstrated the best analytical sensitivity, wherein concordance with real-time PCR was 100%. Legal entity responsible for the study: Kazan Clinical Oncology Center, Kazan, RU Funding: Kazan Clinical Oncology Center, Kazan, RU Disclosure: All authors have declared no conflicts of interest. 154P Plasma dynamic monitoring of soluble c-Met level for EGFR-TKI treatment in advanced non-small cell lung cancer H.-F. Gao, Y.-L. Wu, J.-J. Yang, X.-C. Zhang. Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangzhou, China Background: The activation of c-Met has been associated with both primary and acquired resistance to EGFR-TKI therapy in NSCLC patients. It suggested c-Met status during EGFR-TKI therapy should be concerned. Methods: We retrospectively investigated the dynamic change of soluble c-Met level in plasma and the relationship with the clinical outcomes of EGFR-TKI therapy in advanced NSCLC patients. Immunohistochemistry (IHC) was used to assess the expression of c-Met in the resistant tissue. Plasma c-Met levels were assayed in duplicate using a human soluble c-Met quantitative enzymelinked immunosorbent assay (ELISA) kit. Results: A total of 49 advanced NSCLC patients with EGFR-TKI resistance were selected for the present study. When PD, IHC results showed 37(75.5%) of the patients were tissue c-Met negative, 12 (24.5%) were tissue c-Met positive. There was statistically significant difference in dynamic change of soluble c-Met between tissue c-Met negative group and c-Met positive group (P = 0.002). Patients with baseline soluble c-Met levels > 766 ng/ml showed an inferior median PFS (10.2 vs. 14.0 months, P = 0.003) after EGFR-TKI. Multivariate Cox proportional hazards model analyses demonstrated soluble c-Met level was the independent prognostic factor for PFS after EGFR-TKI (P = 0.009, HR 3.583, 95% CI, 1.379–9.312). Conclusions: uble c-Met in plasma by ELISA provided a noninvasive and sensitive assay to predict EGFR-TKI prognosis. Legal entity responsible for the study: Guangdong Lung Cancer Institute Funding: N/A Disclosure: All authors have declared no conflicts of interest.
Abstracts, ELCC 2016 – Advanced NSCLC
S125
155P PD-L1 polymorphism can predict clinical outcomes of non-small cell lung cancer patients treated with first-line paclitaxel–cisplatin chemotherapy S.K. Do1 , S.Y. Lee2 , J.E. Choi3 , M.J. Hong3 , J.H. Lee4 , J.Y. Park2 . 1 Department of Biochemistry and Cell biology, Kyungpook National University, Daegu, Republic of Korea , 2 Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea, 3 Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea, 4 Departments of Biochemistry and Cell Biology, Kyungpook National University School of Medicine, Daegu, Republic of Korea Background: This study was conducted to investigate whether polymorphisms of genes involved in immune checkpoints can predict the clinical outcomes of patients with advanced stage non-small cell lung cancer (NSCLC) after 1st line paclitaxelcisplatin chemotherapy. Methods: A total of 379 NSCLC patients were enrolled. Twelve single nucleotide polymorphisms (SNPs) of PD-1, PD-L1, and CTLA-4 genes were selected and genotyped. The associations of SNPs with chemotherapy response and overall survival (OS) were analyzed. Results: Among the 12 SNPs investigated, PD-L1 rs2297136T> C and rs4143815C> G were significantly associated with clinical outcomes after chemotherapy. The rs2297136T> C was significantly associated with both better chemotherapy response and better OS, and the rs4143815C> G had a significantly better response to chemotherapy. Consistent with the individual genotype analyses, rs2297136C-rs4143815G haplotype (ht4) carrying variant alleles at both loci was significantly associated with better chemotherapy response and OS compared with combined other haplotypes. Patients with at least one ht4 had significantly better chemotherapy response and OS compared to those without ht4. Conclusions: PD-L1 rs2297136T> C and rs4143815C> G polymorphisms may be useful for the prediction of clinical outcome of 1st line paclitaxel-cisplatin chemotherapy in NSCLC. Further studies are needed to confirm our findings and to understand the role of PD-L1 in the chemotherapy outcome of NSCLC patients. Legal entity responsible for the study: Kyungpook National University Funding: Ministry of Health & Welfare Disclosure: All authors have declared no conflicts of interest. 156P Correlation of baseline value of folate receptor-positive circulating tumor cells and efficacy of pemetrexed and dynamic monitoring study in NSCLC patients receiving first-line platinum-based chemotherapy X. Chen1 , C. Zhou2 , X. Li3 , G. Yang4 . 1 Medical Oncology and Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China , 2 Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China, 3 Dept. of Lung Cancer Immunology, Shangai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China, 4 Research Department, Genosaber Biotec Co. Ltd, Shanghai, China Background: The efficacy of pemetrexed associates with the expression of folate enzymes, however, few serological marker is available to predict its efficacy. Moreover, dynamic monitoring of CTC count can predict the outcome of tumor therapy and the overall survival of the patient. By quantitative determination of folate receptor-positive CTCs, this study investigated the