BACKGROUND METHODS RESULTS Table 1: Baseline Characteristics CONCLUSIONS BIBLIOGRAPHY  The estimated prevalence of EGFR mutations in a representative.

Slides:



Advertisements
Similar presentations
Analysis of the Epidermal Growth Factor Receptor and K-Ras genes in patients with Non-small Cell Lung Cancer H. Mugalaasi1, J. Davies2, L Medley2, D Talbot2,
Advertisements

I I. B.- T R E A T M E N T P L A N: DOCETAXEL 75 mg/m2 40 mg/m2 THORACIC RT (66 Gys: 180 cGy/d) CISPLATIN 40 mg/m2 Days E V A L U A.
Shyamala Maherswaran, Ph.D. et al. Sarah Gomez and Rachael Holmes Detection of Mutations in EGFR in Circulating Lung-Cancer Cells.
Biomarker Analyses in CLEOPATRA: A Phase III, Placebo-Controlled Study of Pertuzumab in HER2- Positive, First-Line Metastatic Breast Cancer (MBC) Baselga.
1 Sitemap Storyflow Title slideOverview slide13.6 months PFSSymptom controlQoL OS across 7 trials3 months OS > 12 month OS Summary slide.
AZD6244 Detection of BRAF Mutations in Tumour and Serum of Patients with Advanced Melanoma Dr Ruth Board CMGS Spring Scientific Conference March 26 th.
Randomized Phase II Trial of Erlotinib (E) Alone or in Combination with Carboplatin/Paclitaxel (CP) in Never or Light Former Smokers with Advanced Lung.
EGFR Mutation Testing From the Pathologist’s Point of View
BRAF mutation analysis in cell free tumoral DNA (cfDNA) of melanoma patients: preliminary results from the Spanish Melanoma Group prospective study GEM1304.
Detection of Mutations in EGFR in Circulating Lung-Cancer Cells Colin Reisterer and Nick Swenson S. Maheswaran et al. The New England Journal of Medicine.
©American Society of Clinical Oncology All rights reserved - American Society of Clinical Oncology Provisional.
Korde N et al. Proc ASH 2014;Abstract 2105.
First-Line TKI Use in EGFR Mutation-Positive NSCLC
A single-arm phase II trial in p treated with C, D and B (15 mg/kg) every 3 weeks followed by B showed a promising efficacy, in terms of progression free.
EGFR Mutation: Clinical Evidence and Resistance to TKIs
Dose Interruption/Reduction of Tyrosine Kinase Inhibitors in the First 3 Months of Treatment of CML Is Associated with Inferior Early Molecular Responses.
Activity and Tolerability of Afatinib (BIBW 2992) and Cetuximab in NSCLC Patients with Acquired Resistance to Erlotinib or Gefitinib Janjigian YY et al.
© 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey Lung Cancer and Gefitinib  Lung cancer statistics in the.
REVISIÓN ESTADIOS IV SEGUNDA LÍNEA “WILD TYPE” Sergio Vázquez Estévez Servicio Oncoloxía Médica Hospital Universitario Lucus Augusti. Lugo Baiona, 25 Abril.
Professor Martin Schuler MD West German Cancer Center Essen, Germany
Treatment of advanced NSCLC:
Final Efficacy Results from OAM4558g, a Randomized Phase II Study Evaluating MetMAb or Placebo in Combination with Erlotinib in Advanced NSCLC Spigel DR.
Cmab might have therapeutic benefit in Japanese patients with KRAS p.G13D mutant colorectal cancer. Limitations of this study are its retrospective design.
Overall survival in NSCLC
. Background Paclitaxel and Irinotecan in Platinum Refractory or Resistant Small Cell Lung Cancer: a Galician Lung Cancer.
Cetuximab plus FOLFIRI in the treatment of metastatic colorectal cancer: the influence of KRAS and BRAF biomarkers on outcome: updated data from the CRYSTAL.
until tumour progression until tumour progression
Who can benefit from chemotherapy holidays after first-line therapy for advanced colorectal cancer ? N. Perez-Staub, B. Chibaudel, A. Figer, A. Cervantes,
Crizotinib outcomes in ALK- positive advanced NSCLC patients with brain metastases 1 RTI Health Solutions, Research Triangle Park, NC/United States of.
Clinicopathologic Features of EML4-ALK Mutant Lung Cancer Shaw AT et al. ASCO 2009; Abstract (Poster)
Personalized medicine in lung cancer R4 김승민. Personalized Medicine in Lung Cancer patients with specific types and stages of cancer should be treated.
Mok TS, Wu SL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361: Gefitinib Superior.
Erlotinib plus Gemcitabine Compared with Gemcitabine Alone in Patients with Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute.
Genomic Medicine Rebecca Tay Oncology Registrar. What is Genomic Medicine? personalised, precision or stratified medicine.
Certinib in ALK-Rearranged Non- Small-Cell Lung Cancer Alice T. Shaw, M.D., Ph.D., Dong-Wan Kim, M.D., Ph.D., Ranee Mehra, M.D., Daniel S.W. Tan, M.B.,
Cancer targeted therapy José Carlos Machado. Cancer progression.
Pooled analysis of clinical outcomes in studies of patients with EGFR mutations treated with either an EGFR TKI or chemotherapy Luis Paz-Ares 1, Denis.
1 LUX-Lung 3 clinical trial ECOG=Eastern Cooperative Oncology Group. Sequist LV et al. J Clin Oncol. 2013;31(27): Treatment-naïve Advanced NSCLC.
Lung Cancer in Never-Smokers from the Princess Margaret Cancer Centre 1 Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada;
Blood-based biomarkers for cancer immunotherapy: Tumor mutational burden in blood (bTMB) is associated with improved atezolizumab (atezo) efficacy in.
EGFR mutation in Austrian patients with NSCLC: a retrospective study
LUX-Lung 6 clinical trial
LUX-Lung 3 clinical trial
Fig. 1. EGFR content as determined by fluorescence in situ hybridization (FISH) and immunohistochemical staining. FISH was performed with the EGFR ( red.
Fig. 2. High-resolution melting curves for exon 21 of the EGFR gene
Rosell R et al. Proc ASCO 2011;Abstract 7503.
Fig 1A. Patient enrollment flow chart
Prognostic impacts of EGFR mutation status and subtype in patients with surgically resected lung adenocarcinoma  Kazuya Takamochi, MD, Shiaki Oh, MD,
Treatment With Continuous, Hyperfractionated, Accelerated Radiotherapy (CHART) For Non-Small Cell Lung Cancer (NSCLC): The Weston Park Hospital Experience.
Prognosis of younger patients in non-small cell lung cancer
Verstovsek S et al. Proc ASH 2011;Abstract 793.
“CASE SERIES OF EGFR MUTATIONS IN SQUAMOUS CELL CARCINOMA LUNG ”
Patient Case 1 Patient Case 1: PET/CT Scan.
Crystal digital PCR for detection and quantification of circulating EGFR mutations in advanced non-small cell lung cancer Cécile Jovelet Postdocoral fellow.
Unità Clinica di Diagnostica Istopatologica e Molecolare
until tumour progression until tumour progression
The New Taxonomy of Metastatic NSCLC and Physician Treatment Based on Pathologic and Molecular Characteristics The New Taxonomy of Metastatic Non-Small.
Regulatory Industry Statistics Workshop 2018
Monitoring EGFR mutation status in Non-small cell lung cancer (NSCLC) patients using circulating Tumour DNA (ctDNA). Matthew Smith Molecular Pathology.
T790M Mutation-Positive NSCLC: A Multidisciplinary Case Conference
EGFR Molecular Profiling in Advanced NSCLC: A Prospective Phase II Study in Molecularly/Clinically Selected Patients Pretreated with Chemotherapy  Michele.
Kaplan–Meier curves of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) progression-free survival (PFS) were constructed based on.
Detection rate for EGFR mutations in cfDNA.
Clinical courses of patients.
A Prospective, Molecular Epidemiology Study of EGFR Mutations in Asian Patients with Advanced Non–Small-Cell Lung Cancer of Adenocarcinoma Histology (PIONEER) 
Cetuximab with chemotherapy as 1st-line treatment for metastatic colorectal cancer: a meta-analysis of the CRYSTAL and OPUS studies according to KRAS.
(A) Survival time. (A) Survival time. All patients. (a) PFS since the start of EGFR-TKI (groups A, B and C). (b) OS since the start of EGFR-TKI (groups.
Jessica J. Lin, MD, Stephanie Cardarella, MD, Christine A
XL647—A Multitargeted Tyrosine Kinase Inhibitor: Results of a Phase II Study in Subjects with Non-small Cell Lung Cancer Who Have Progressed after Responding.
Presentation transcript:

BACKGROUND METHODS RESULTS Table 1: Baseline Characteristics CONCLUSIONS BIBLIOGRAPHY  The estimated prevalence of EGFR mutations in a representative sample of newly diagnosed advanced NSCLC patients in Galicia is consistent with previous data obtained in the rest of Spain  EGFR mutation testing was possible in more than 90% of patients.  Given the similar adequacy for molecular analysis and mutation rates observed in cytological vs. tissue samples, cytologies should be considered suitable for mutation analysis.  The median TAT of 8 days to establish the EGFR mutation status allows the customization of treatment based on molecular criteria  EGFR testing in serum has a low sensitivity and therefore should not substitute tissue testing although it could be an alternative for those patients without tissue samples.  More than 90% of patients receive first line treatment, most of them received a TKI  Comparison EGFR mutational status between baseline and disease progression could not be done because no obtional tumor samples were obtained at progression. Table 2: Sample source and type Figure 2: EGFR Mutation Rates by Clinical features OBSERVATIONAL POST-AUTHORIZATION PROSPECTIVE STUDY TO CHARACTERIZE THE INCIDENCE OF EGFR POSITIVE MUTATION (M+) IN ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER (aNSCLC) PATIENTS (P) AND THEIR CLINICAL MANAGEMENT IN GALICIA (NCT ): A GALICIAN LUNG CANCER GROUP STUDY (GGCP ) Sergio Vázquez Estévez 1, Joaquín Casal Rubio 2, Javier Afonso Afonso 3, José Luis Fírvida Pérez 4, Lucía Santomé Couto 5, Francisco Barón Duarte 6, Martín Lázaro Quintela 7, Carolina Pena Álvarez 8, Margarita Amenedo Gancedo 9, Ihab Abdulkader Nallib 6, Carmen González Arenas 10, Laura Fachal 11, Ana Vega 11 1 Hospital Universitario Lucus Augusti (Lugo); 2 Complexo Hospitalario Universitario de Vigo (Pontevedra); 3 Hospital Arquitecto Marcide de Ferrol (A Coruña); 4 Complexo Hospitalario Universitario de Ourense; 5 Hospital Povisa de Vigo (Pontevedra); 6 Complexo Hospitalario Universitario de Santiago (A Coruña); 7 Complexo Hospitalario Universitario de Vigo (Pontevedra); 8 Complexo Hospitalario de Pontevedra; 9 Centro Oncolóxico de Galicia (A Coruña); 10 AstraZeneca, Madrid, Spain; 11 Fundación Pública Galega de Medicina Xenómica-SERGAS, Santiago de Compostela, Spain The presence of mutations in the gene encoding the Epidermal Growth Factor Receptor (EGFR) predicts that P with aNSCLC may respond better to Tyrosine Kinase Inhibitors (TKIs )1-4. Recently, the Spanish study REASON has reported that the rate of EGFR mutations is 11.6% in Spain 5, however the mutation rate and the clinical management of aNSCLC patients carrying EGFR mutations in Galicia are still unknown. OBJECTIVES  Primary Objective:  To characterize the number of patients with epidermal growth factor receptor (EGFR) positive mutations among advanced or metastatic non-small cell lung cancer (NSCLC) patients in Galicia  Secondary Objective:  To describe the type of mutations among NSCL EGFR M+ patients.  To describe the clinical management of EFGR M+ patients.  To describe patterns of EGFR mutations after progression of EGFR M+ patients.  To correlate EGFR mutational status in tumour and serum samples.  To compare EGFR mutational status between baseline and disease progression of EGFR M+ patients.  All newly diagnosed aNSCLC patients in 9 Galician centres were prospectively included for a 13-month period.  Patients with M+ disease were followed from inclusion until disease progression, death or until 9 months from the inclusion of the last patient in the study have elapsed, whichever is earlier, for the characterization of their clinical management Figure 1: Flowchart CharacteristicTotal Patients N=198 SexMale151 (76.3%) Female47 (23.7%) AgeMedian65.5 years HistologySquamous43 (21.7%) Adenocarcinoma136 (68.7%) Large cells Carc.16 (8.1%) Adenosquamous2 (1.0%) NOS1 (0.5%)  From February 2011 to March 2012 a total of 198 patients were enrolled  Mutation analysis in tissue samples was feasible in 184 P (92.93%) CharacteristicTotal Patients N=198 Smoking statusNever smoked43(21.7%) Ex-smoker90(45.5%) Smoker65 (32.8%) WHO PS027 (13.6%) 1106 (53.5%) 249 (24.7%) ≥ 316 (8.1%) Table 3: Turn Around Time (TAT) Median: 8 Working days Average: 10.3 days Table 4: Mutation frequency by sample type EGFR StatusTotal N=184 (%) Biopsy N=108 Cytology N=76 EGFR +25 (13.6%)15 (13.9%)10(13.2%) EGFR -159 (86.4%)93 (86.1%)66 (86.8%) Patients EGFR M+N=2513.6% 1 Exon 1800% 2 Exon % 2 Del 1911 Exón 2028% 2 Exon 20 insertions1 Not specificed1 Exon % 2 L858R11 L681Q1 Table 5: Types of Mutation (1)Percentage calculated considering n=184 samples evaluable for EGFR Status; (2)Percentage according to Patients EGFR M+ Figures 3 & 4: Line of Treatment for Patients EGFR M+ Figure 5: First Line Treatment Response rate Out of the 23 patients that underwent treatment 3 were excluded due to lost of follow up and only 20 were evaluated Figures 6 and 7: PFS & OS For Patients EGFR M+ (n= 20 ) #1695  Mutation testing was performed on available tumour and serum samples, through a central laboratory using the EGFR RGQ PCR Kit TM (Qiagen)  Pre-planned exploratory objectives included comparison of EGFR mutation status between matched baseline tumour and plasma samples 95% CI Median (months) ,0 0,8 0,6 0,4 0,2 0, Time from first linetreatment (months) Estimated probality of overall survival Overall survival (OS) Progression free survival (PFS) 1,0 0,8 0,6 0,4 0,2 0, Estimated probability of PFS Median (months) 95% CI month PFS: 37% (95% CI: ) Time from first line treatment (months) 1.Mok TS et al. N Engl J Med 2009;361: Maemondo M et al. N Engl J Med 2010;362: Mitsudomi T et al. Lancet Oncol 2010;11: Rosell R et al. N Engl J Med 2009;13: Massuti B et al. J Thorac Oncol 2011; 5 (Suppl 2): S329-S330, Abs.O Rekhtman N, et al. J Thorac Oncol 2011; 6: 451–458. ACKNOWLEDGEMENTS Patients and families, investigators, data managers, lab staff. Poster presented at 15 th WCLC, October October, Sydney, AustraliaThis study was supported by AztraZeneca through the Investigators Sposored Studies programme EGFR status at baseline Serum mutation status EGFR +EGFR -Total Tumor mutation status EGFR EGFR Total * Table 6: Comparison of baseline tumour EGFR mutation status with evaluable results from baseline serum Concordance rate90.8% Sensitivity40% Specificity99.3% Positive predictive value (PPV)90.9% Negative predictive value (NPV)90.8% *Summary of EGFR status for tumour and serum samples from patients who are evaluable for both samples.