Journal Thoracic Oncology

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Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017 Keywords: NSCLC, squamous cell, EGFR mutation POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ IMMUNOTHERAPY EGFR – WEDNESDAY, DECEMBER 7, 2016 P3.02B-005 PHASE IB TRIAL OF AFATINIB AND BI 836845 IN ADVANCED NSCLC: DOSE ESCALATION AND SAFETY RESULTS Keunchil Park 1 , Byoung Chul Cho 2 , Ki Hyeong Lee 3 , Wu-Chou Su 4 , Sang-We Kim 5 , Chia-Chi Lin 6 , Dennis Chin-Lun Huang 7 , Helen Hayoun Jung 8 , Yuan Geng 9 , Daniel Shao Weng Tan 10 1 Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul/ Korea, Republic of, 2 Yonsei University Medical Center, Seoul/Korea, Republic of, 3 Chungbuk National University Hospital, Cheongju/Korea, Republic of, 4 National Cheng Kung University Medical College and Hospital, Tainan/Taiwan, 5 Asan Medical Center, University of Ulsan College of Medicine, Seoul/Korea, Republic of, 6 National Taiwan University Hospital, Taipei/Taiwan, 7 Boehringer Ingelheim Taiwan Limited, Taipei/Taiwan, 8 Boehringer Ingelheim Korea, Seoul/Korea, Republic of, 9 Boehringer Ingelheim (China) Investment Co., Ltd, Shanghai/China, 10 National Cancer Centre, Singapore/Singapore Background: Insulin-like growth factor (IGF) signaling is implicated in acquired resistance to EGFR TKIs in NSCLC. BI 836845 is an IGF ligand-neutralizing antibody that binds to IGF-1 and IGF-2, and inhibits their growth-promoting activities. This Phase Ib trial evaluates BI 836845 in combination with afatinib in patients with NSCLC progressing following prior treatment with EGFR TKIs or platinum-based chemotherapy (NCT02191891). Methods: The trial consists of two sequential parts: a dose confirmation part (Part A, reported here) and an expansion part (Part B). In Part A, eligible patients were aged ≥18 years with advanced and/or metastatic NSCLC progressing on EGFR TKIs (patients with EGFR mutations) or platinum-based chemotherapy. Patients receiving prior afatinib therapy below the assigned dose level or
Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017 and 63 were females. 127 patients (90.1%) were ECOG 0-1 while 14 patients (9.1%) were ECOG >1. Exon 21 mutation was present in 65 patients (46.1%) and exon 19 mutation in 76 patients (53.9%). 133 of 141 patients were evaluable for response. Response rate of patients having exon 19 mutation was 72.9% (51 patients, n=70) while it was 55.6% in patients having exon 21 mutation (35 patients, n=63) {p=0.046}. Median PFS in exon 19 mutated patients was 9.3 months (95% CI 6.832-11.768) compared to 7.8 months (95% CI 5.543-10.047) in exon 21 mutated patients (p=0.699). The median OS in exon 19 mutated patients was 19.8 months (95 % CI 16.8-22.7) and 16.5 months (95% CI 10.9- 22.1) in exon 21 mutated patients (p=0.215).Only female gender had a positive impact on both PFS and OS on multivariate analysis. Keywords: gefitinib, EXON, NSCLC, survival POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ IMMUNOTHERAPY EGFR BIOMARKERS – WEDNESDAY, DECEMBER 7, 2016 P3.02B-008 QUANTIFICATION AND MONITORING OF TREATMENT RESPONSE IN EGFR MUTANT NSCLC PATIENTS BY DIGITAL-PCR IN PLASMA CFTDNA Vienna Ludovini 1 , Annamaria Siggillino 1 , Maria Sole Reda 1 , Fortunato Bianconi 2 , Rita Chiari 1 , Sara Baglivo 1 , Lorenza Pistola 1 , Francesca Romana Tofanetti 1 , Roberta Matocci 1 , Clelia Mencaroni 1 , Giulio Metro 1 , Chiara Bennati 1 , Vincenzo Minotti 1 , Lucio Crinò 1 1 Medical Oncology, Santa Maria Della Misericordia Hospital, Azienda Ospedaliera Di Perugia, Perugia/Italy, 2 Department of Experimental Medicine, University of Perugia, Perugia/Italy Background: The identification of activating epidermal growth factor receptor (EGFR) mutations is essential for deciding therapy of non-small cell lung cancer (NSCLC) patients. Circulating cell-free tumor DNA (cftDNA) holds promise as a non-invasive methodology for tumor monitoring in solid malignancies. Among advanced NSCLC patients with an acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs), about 50% carry T790M mutation, but its frequency in EGFR-TKI-naıve patients and dynamic change during therapy remains unclear. We hypothesized that EGFRmutation analysis detection in cftDNA for NSCLC may be feasible for monitoring treatment response to EGFR-TKIs and also predict drug resistance. Methods: EGFR sensitive mutations and T790M were analyzed using digital PCR (d-PCR) (Quant studio 3D, life technologies) in longitudinally (at baseline, at 4, 8, 20, 60, 120, 180, 270, 360 days) collected plasma samples (n=50) from 8 tissue-confirmed EGFRmutant NSCLC patients treated with an EGFR-TKI (Gefitinib N = 4; Erlotinib N = 1; Afatinib N = 3). DNA extracted from plasma of 8 healty blood donors were used to detect the specificity of EGFR mutant assay. Tumor assessment was performed according to RECIST criteria 1.1 every two months. Results: The sensitivity of d-PCR in plasma versus tissue was 71.4%. No EGFR mutation was present in the 8 control cases (specificity of 100%). Of four patients who developed progression disease (PD), in the samples of progression, T790M was detected in 75% of cases. The frequency of T790M in pre-TKI plasma samples was of 37.5%. EGFR sensitive mutations decreased at PD while T790M mutation increased in 75% of patients. Patients with concomitant pre-TKI EGFR 19 deletion and T790M showed a PD before of 12 months compared to those with L858R. T790M was frequently detected when new lesions were developed. Four patients had T790M level decreased to undetectable level with longer PFS than those with detectable T790M in blood. Conclusion: Our results indicated that d-PCR was a highly sensitive and useful method for detecting the T790M mutation. Moreover, dynamically monitoring T790M change might help determining EGFR-TKI resistance. We thank Italian Association for Cancer Research (AIRC) for supporting the study. Keywords: cftDNA, advanced NSCLC, digital PCR, resistance to EGFR-TKIs POSTER SESSION 3 – P3.02B: ADVANCED NSCLC & CHEMOTHERAPY/TARGETED THERAPY/ IMMUNOTHERAPY EGFR BIOMARKERS – WEDNESDAY, DECEMBER 7, 2016 P3.02B-009 PLASMA AND TISSUE INFLAMMATORY AND ANGIOGENIC BIOMARKERS TO EXPLORE RESISTANCE TO EGFR- TKIS AND ASSOCIATION WITH VERISTRAT STATUS Elena Brioschi 1 , Francesca Corti 1 , Chiara Lazzari 1 , Silvia Foti 1 , Olga Nigro 1 , Angelo Corti 2 , Claudio Doglioni 3 , Luisella Righi 4 , Alessandra Bulotta 1 , Mariagrazia Viganò 1 , Monica Ducceschi 1 , Valter Torri 5 , Luca Porcu 5 , Fred R. Hirsch 6 , Heinrich Roder 7 , Silvia Novello 8 , Luca Gianni 1 , Vanesa Gregorc 1 1 Oncology, Istituto Di Ricovero E Cura A Carattere Scientifico, Ospedale San Raffaele, Milano/Italy, 2 Tumor Biology and Vascular Targeting, Istituto Di Ricovero E Cura A Carattere Scientifico, Ospedale San Raffaele, Milano/Italy, 3 Pathology, Istituto Di Ricovero E Cura A Carattere Scientifico, Ospedale San Raffaele, Milano/ Italy, 4 Department of Pathology, University of Turin, Aou San Luigi, Orbassano/ Italy, 5 Oncology, IRCCS-Istituto Di Richerche Farmacologiche Mario Negri, Milano/ Italy, 6 Department of Medical Oncology, University of Colorado Denver, Aurora/CO/ United States of America, 7 Biodesix, Inc., Steamboat Springs/CO/United States of America, 8 Department of Oncology, University of Turin, Aou San Luigi, Orbassano/ Italy Background: VeriStrat is a proteomic test validated to be prognostic and predictive of overall survival (OS) to EGFR Tyrosine Kinase Inhibitors (TKIs) in EGFR wild type patients 1 . Serum Amyloid A1 (SAA1) and its two truncated forms are responsible for 4 of the 8 peaks overexpressed in Veristrat (VS) Poor classified patients. The aim of the study was to explore if the microenvironment, with its complex network mediated by inflammation and angiogenesis could represent the base of the aggressive disease behavior of VS Poor subjects. Moreover, the activity of the immune escape axis PD-1/PD-L1 was explored. Methods: Plasma biomarkers analyses were retrospectively performed on plasma baseline samples of 244 patients enrolled in the PROSE trial 1 , while exploratory tissue analysis was performed on 37 available histological specimens. Circulating levels of HGF, VEGF, FGF, Cromogranin A (CgA) and its pro- and anti-angiogenic fragments (fragment 1-373 and 1-76, respectively) were determined by an ELISA assay. PD-L1 expression both on tumor cells and inflammatory elements of the tumor microenvironment, and the tissue expression (T) of HGF and its receptor c-MET were measured by immunohistochemistry. Results: CgA, HGF, VEGF, and FGF plasma levels were statistically significantly higher in VS Poor subjects. High plasma HGF levels were associated with lower PFS (3.4 versus 2.0 months, HR 1.67; 95% CI 1.25-2.23; p
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LILLY ONCOLOGY IS DEDICATED TO ADVA
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