OTRAS DIANAS MOLECULARES TRATABLES. Rosario García Campelo Servicio de Oncología Médica Complejo Hospitalario Universitario A Coruña, CHUAC
|
|
- Martina Marsh
- 5 years ago
- Views:
Transcription
1 OTRAS DIANAS MOLECULARES TRATABLES Rosario García Campelo Servicio de Oncología Médica Complejo Hospitalario Universitario A Coruña, CHUAC
2 A propósito de un caso. Mujer 34 años Fumadora ocasional < 10 paq/año Dx de Adenocarcinoma de pulmón ctxn3m1b, estadio IV EGFR WT ALK WT PE tras CDDP+Pemetrexed PE tras Docetaxel PS 0-1 Y ahora qué?...
3 THE SO LIMITED OTHERS CONCEPT Targetable oncogenes in lung ADC Minuti G et al. Exp Opin Biol Ther 2013; 13(10):
4 The so low frecuency Mostly non-overlapping Never/ light smokers (exceptions: KRAS, BRAF) Growing understanding of resistance mechanisms Gerber D et al. Educational Book ASCO 2014
5 Rationale for targeting the ROS receptor tyrosine kinase FN-III-like repeats TK domain Structure of ROS ROS overexpression in brain, lung, gastric, breast, and liver tumors/cell lines ROS mutations in colon and kidney cancer cell lines ROS fusions identified in cancer Glioblastoma: FIG-ROS1 NSCLC: SCL34A2-, CD74-, FIG-, SDC4-,TPM3-, ERZ-,LRIG3-ROS1 Cholangiocarcinoma: FIG-ROS1 Drosophila homolog: sevenless Drosophila ligand homolog: son of sevenless Growth of cell lines with ROS fusion genes inhibited by crizotinib El-Deeb et al., Med Res Rev. 2010
6
7 ROS1 Rearrangements in NSCLC TPM3-ROS1 SDC4-ROS1 SLC34A2-ROS1 CD74-ROS1 EZR-ROS1 Present in ~1% of NSCLC cases (also found in some GBMs and cholangiocarcinomas) Enriched in younger never or light smokers with adenocarcinoma histology No overlap with other oncogenic drivers LRIG3-ROS1 ROS1 Bergethon et al., JCO 30(8): , 2012; Takeuchi et al., Nat Med 18(3): , 2012
8 Study 1001: Clinical Characteristics of Patients with ROS1-positive NSCLC Characteristic Crizotinib (N=42) Age, years Median (range) 52 (31 77) Sex, n Male/female 19/23 Smoking history, n (%) Never 33 (79) Former 9 (21) Race, n (%) Caucasian 21 (50) Asian 18 (43) Other 3 (7) Histology, n(%) Adenocarcinoma 41 (98) a ECOG PS, n (%) 0 21 (50) 1 20 (48) 2 1 (2) b Prior regimens for None 6 (14) advanced/metastatic 1 regimen 18 (43) disease, n (%) >1 regimen 18 (43) a Includes one patient with adenocarcinoma-favored, poorly differentiated NSCLC b Patient had an ECOG PS of 1 at screening and 2 on cycle 1 day 1 Ou S-HI, et al. J Thorac Oncol 2013;8(Suppl 2):S295 (Presentation MO07.03)
9 Best change from baseline (%) Study 1001: Best Tumor Responses in Evaluable Patients with Advanced ROS1-positive NSCLC a evaluable patients; 2 CRs and 20 PRs Overall response rate: 61% (95% CI: 44 77) Disease control rate: 81% (8 weeks), 67% (16 weeks) Best overall response * PD SD PR CR 100 +Treatment ongoing; duration of response/sd is from first documentation of tumor response/first dose to the time of PD or death. For ongoing patients, duration of response/sd is from first documentation of tumor response/first dose to last available on-treatment scan Duration is in weeks a Excludes patients with early death (n=2) *This patient was ALK+ Data as of April 24, 2013 Ou S-HI, et al. J Thorac Oncol 2013;8(Suppl 2):S295 (Presentation MO07.03)
10 PFS Probability Study 1001: PFS in Patients with ROS1-positive NSCLC (N=42) Median PFS not reached 26 patients (62%) still in follow-up for progression Event-free probability: 76% (95%CI: 55 88) at 6 months Number at risk Censored 95% Hall-Wellner Time Band (months) Ou S-HI, et al. J Thorac Oncol 2013;8(Suppl 2):S295 (Presentation MO07.03)
11 Epidemiology HER2 mutation 403 stage I-III adenocarcinomas in caucasian patients: mutation in 9 (2.2%). 78% in frame duplications insertions in exon 20 Frequency higher in females and in never smokers 394 adenocarcinoma, HER2 mutations preferentially in oriental ethnicity (3.9% vs 0.7%) All HER2 mutations were in-frame insertions in exon 20, significantly more frequent in never smokers and adenocarcinoma 6% of EGFR/KRAS/ALK-negative specimens More frequent among never-smokers but no associations with sex, race, or stage HER2 mutation was not associated with concurrent HER2 amplification p: HER2 mut in 1.7%, all insertions in exon 20, 69% women, neversmokers 52.3% Buttitta, Int J Cancer 2006, Shigematsu, CCR 2005, Arcila CCR 2012, Mazieres JCO 2013
12 Therapeutic Perspectives 68.2 m 22.9 m 22 patients receiving anti HER2 therapy ORR: 50% DCR 82% Median PFS: 5.1m DCR Trastuzumab based therapies (n= 15): 96% DCR Afatinib based therapy (n=4): 100% No responses to lapatinib or to masatinib Mazieres JCO 2013
13 KRAS mutation: PROGNOSTIC, PREDICTIVE OR DRUGGABLE 2nd most common mutation in human cancer 677 patients with advanced NSCLC and KRAS mutation seen at the MSKCC between 2005 and 2011 Lung Cancer: mutation at codon 12,13, 61 Smokers: G12C,G12V A greater oncogenic potential for KRas G12V compared to other mutations Non smokers: G12D Yu A J Clin Oncol 2013 Abstr 8025
14
15 MEKi (Selumetinib or Trametinib) plus docetaxel for KRAS mutant advanced NSCLC Jänne, Lancet Oncol 2013 Gandara D et al. J Clin Oncol 2013 Abstr 8028
16 LY (Abemaciclib): a cell cycle inhibitor CDK4 and CDK6 Goldman et al. J Clin Oncol 2014 Abstr 8026
17 DIRECT KRAS G12C INHIBITORS Lim SM et al. Angew Chem Int Ed 2014
18 SUMMARIZE OF CURRENT STRATEGIES TARGETING KRAS MUT NSCLC PATIENTS Vasan et al. Clin Cancer Res 2014
19 1046 NSCLC 4.9% ADC 0.3% SCC More common in current /former smokers V % (more diverse mutation profile than in melanoma) V600 more prevalent in females: 8.6% vs 0.9% V600 showed agressive histotype and shorter PFS and OS
20 Activity of BRAF inhibitors in BRAF mut NSCLC patients Best response n=20 Complete response (CR), n (%) 0 Partial response (PR), n (%) 8 (40) Stable disease (SD), n (%) 4 (20) Progressive disease, n (%) 6 (30) Not evaluable, n (%) 2 (10) Response rate (confirmed CR/PR), % (95% CI) Disease control rate (CR + PR + SD), % (95% CI) 40 ( ) 60 ( ) Response to Dabrafenib in a V600E mutated NSCLC patient Rudin et al. JTO 2013 Planchard et al. ASCO 2013
21 Incidence (%) RET: a new kid on the rock KIF5B, CCDC6 Incidence of RET fusions Never-Smokers Pan-Negative Lung AdenoCAs Vandetanib, sorafenib, sunitinib, cabozantinib have RET activity Pan-Negative NSCLCs 1% of lung cancer Unselected NSCLCs 95% CI [3 27%] n=5/34 Lipson et al 1 Nature 2012 Wang et al 2 JCO 2012 Drilon et al Cancer Discovery 2013
22 Met alterations in cancer X DNA RNA Protein MET gene copy alterations (amplification or polisomy) MET gene mutations MET RNA over expression Met protein overexpression Met porttranslational modifications (e.g. phosphorylation)
23 C-MET receptor tyrosine kinase Amplified, mutated, and overexpressed in many tumors Associated with worse prognosis in NSCLC MARQUEE TRIAL Met activation, implicated in resistance to EGFR inhibition MET inhibitors in NSCLC: ARQ 197 and MetMAb MET LUNG TRIAL Erlotinib/placebo v erlotinib/arq 197 NEGATIVE Erlotinib/placebo v erlotinib/metmab Met inhibitor TKI, daily PO Mab, Iv q 3W Trial phase, design Randomised Phase II, Placebo Randomised Phase II, Placebo N pts Eligibilitty > 1 prior line 2 nd -3rd line Tissue required End-point PFS PFS-all pts PFS in Met High pts
24 Crizotinib is a first-in-class, potent and selective ATP competitive inhibitor of c-met Kinase IC50 (nm) mean* Selectivity ratio Met 8 ALK X ROS 55 7X RON 80 10X X Axl X Tie X Abl 1, X IRK 2, X Lck 2, X Sky >10,000 >1000X VEGFR2 >10,000 >1000X PDGFRβ >10,000 >1000X Camidge et al. J Clin Oncol 2014 Abstr 8001
25 Squamous cell lung cancer: The forgotten one A significant minority of NSCLC No effective targeted therapy Lack of efficacy or toxicity for Pemetrexed Bevacizumab Some KRAS and PIK3CA mutations Ongoing systematic genomics efforts The Cancer Genome Atlas
26 Dominant Mutations in Lung Cancer Some time ago KRAS EGFR EML4-ALK BRAF PIK3CA ERBB2 Other Lung adenocarcinoma Lung squamous cell carcinoma
27 Genetic alterations in SCC 2014 Perez-Moreno et al. CCR 2012
28 Dasatinib shrinks DDR2-mutant tumors in vivo Discoidin death receptor 2 (DDR2) Mutation in 4% SCC and 1% NSCC Dasatinib has shown preclinical and clinical activity Hammerman et al. Cancer Discovery 2011
29 FGFR1 amplification occurs in 20% of primary squamous-cell lung cancers Weiß et al. Science Trans Med 2010
30 Targeting FGFR1 in SCC FGFR-amplified NSCLC BGJ398 AZD4547 Nogora et al. J Clin Oncol 2014 Abstr 8034 Paik et al. J Clin Oncol 2014 Abstr 8035 Not a true driver? Cutoff for amplification? Tumor heterogeneity?
31 Clinical application of molecular subsets is not easy, however...
32 A propósito de un caso. PE tras CDDP+Pemetrexed PE tras Docetaxel 34 años, PS 0-1 No muestra tumoral disponible para análisis molecular Y ahora qué?... Re-biopsia adenopatía retroperitoneal: Kras negativo BRAF- FISH HER2 negativo Ros negativo MET: 3 (+) 65% (positivo) por IHQ
33 H&E IHQ MET
34 The complex history of other genomic alterations in our daily practice The Cancer Biomarker Problem Rebiopsies procedures at different moments of the disease evolution New technologies (NGS, WGS ) Are we using the right biomarker? Cost What should I do if after all this effort I find a genetically defined NSCLC patient?
35 EMERGING TECHNOLOGIES FOR TUMOR GENOMIC PROFILING MacConaill L E JCO 2013;31:
36 NGS to identify genomic alterations in pan negative lung cancer patients 1 genomic alteration identified in 94% of patients Tumor tested was obtained from the same procedure as tumor used for non-ngs testing in 71% of cases Drilon et al. J Clin Oncol 2014 Abstr 8029
37 LCMC: Molecular characterization network and associated clinical trials
38 Some notes to conclude many targets, many drugs A pletora of new agents in the horizon that target specific molecularly defined patients, let s say PERSONALIZED THERAPY: Establish molecular profile Availability of tumor tissue Newer technologies allow testing all of these mutations at the same time Some of these genetic alterations have a low incidence, but Every single patient is unique: it s worthwhile
Beyond ALK and EGFR: Novel molecularly driven targeted therapies in NSCLC Federico Cappuzzo AUSL della Romagna, Ravenna, Italy
Beyond ALK and EGFR: Novel molecularly driven targeted therapies in NSCLC Federico Cappuzzo AUSL della Romagna, Ravenna, Italy Oncogenic drivers in NSCLC Certain tumours arise as a result of aberrant activation
More informationThe oncologist s point of view: the promise and challenges of increasing options for targeted therapies in NSCLC
The oncologist s point of view: the promise and challenges of increasing options for targeted therapies in NSCLC Egbert F. Smit Department of Thoracic Oncology, Netherlands Cancer Institute, and Department
More information2 nd line Therapy and Beyond NSCLC. Alan Sandler, M.D. Oregon Health & Science University
2 nd line Therapy and Beyond NSCLC Alan Sandler, M.D. Oregon Health & Science University Treatment options for advanced or metastatic (stage IIIb/IV) NSCLC Suitable for chemotherapy Diagnosis Unsuitable/unwilling
More informationK-Ras signalling in NSCLC
Targeting the Ras-Raf-Mek-Erk pathway Egbert F. Smit MD PhD Dept. Pulmonary Diseases Vrije Universiteit VU Medical Centre Amsterdam, The Netherlands K-Ras signalling in NSCLC Sun et al. Nature Rev. Cancer
More informationMolecular Targets in Lung Cancer
Molecular Targets in Lung Cancer Robert Ramirez, DO, FACP Thoracic and Neuroendocrine Oncology November 18 th, 2016 Disclosures Consulting and speaker fees for Ipsen Pharmaceuticals, AstraZeneca and Merck
More informationTargeted therapies for advanced non-small cell lung cancer. Tom Stinchcombe Duke Cancer Insitute
Targeted therapies for advanced non-small cell lung cancer Tom Stinchcombe Duke Cancer Insitute Topics ALK rearranged NSCLC ROS1 rearranged NSCLC EGFR mutation: exon 19/exon 21 L858R and uncommon mutations
More informationLung Cancer Genetics: Common Mutations and How to Treat Them David J. Kwiatkowski, MD, PhD. Mount Carrigain 2/4/17
Lung Cancer Genetics: Common Mutations and How to Treat Them David J. Kwiatkowski, MD, PhD Mount Carrigain 2/4/17 Histology Adenocarcinoma: Mixed subtype, acinar, papillary, solid, micropapillary, lepidic
More information7/6/2015. Cancer Related Deaths: United States. Management of NSCLC TODAY. Emerging mutations as predictive biomarkers in lung cancer: Overview
Emerging mutations as predictive biomarkers in lung cancer: Overview Kirtee Raparia, MD Assistant Professor of Pathology Cancer Related Deaths: United States Men Lung and bronchus 28% Prostate 10% Colon
More informationOTRAS TERAPIAS BIOLÓGICAS EN CPNM: Selección y Secuencia Óptima del Tratamiento
OTRAS TERAPIAS BIOLÓGICAS EN CPNM: Selección y Secuencia Óptima del Tratamiento Dolores Isla Servicio de Oncología Médica HCU Lozano Besa de Zaragoza 2008 Selection Factors in Advanced NSCLC ( 8y ago)
More informationDisclosures Genomic testing in lung cancer
Disclosures Genomic testing in lung cancer No disclosures Objectives Understand how FISH and NGS provide complementary data for the evaluation of lung cancer Recognize the challenges of performing testing
More informationMolecular Testing in Lung Cancer
Molecular Testing in Lung Cancer Pimpin Incharoen, M.D. Assistant Professor, Thoracic Pathology Department of Pathology, Ramathibodi Hospital Genetic alterations in lung cancer Source: Khono et al, Trans
More informationLUNG CANCER. pathology & molecular biology. Izidor Kern University Clinic Golnik, Slovenia
LUNG CANCER pathology & molecular biology Izidor Kern University Clinic Golnik, Slovenia 1 Pathology and epidemiology Small biopsy & cytology SCLC 14% NSCC NOS 4% 70% 60% 50% 63% 62% 61% 62% 59% 54% 51%
More informationPersonalized Medicine: Lung Biopsy and Tumor
Personalized Medicine: Lung Biopsy and Tumor Mutation Testing Elizabeth H. Moore, MD Personalized Medicine: Lung Biopsy and Tumor Mutation Testing Genomic testing has resulted in a paradigm shift in the
More informationAntiangiogenic Agents in NSCLC Where are we? Which biomarkers? VEGF Is the Only Angiogenic Factor Present Throughout the Tumor Life Cycle
Antiangiogenic Agents in NSCLC Where are we? Which biomarkers? Martin Reck Department e t of Thoracic c Oncology ogy Hospital Grosshansdorf Germany VEGF Is the Only Angiogenic Factor Present Throughout
More informationALK Inhibition: From Biology to Approved Therapy for Advanced Non-Small Cell Lung Cancer
ALK Inhibition: From Biology to Approved Therapy for Advanced Non-Small Cell Lung Cancer Dr. Ben Solomon Medical Oncologist, Thoracic Oncology Peter MacCallum Cancer Centre Melbourne, Australia Dr. D.
More informationVirtual Journal Club: Front-Line Therapy and Beyond Recent Perspectives on ALK-Positive Non-Small Cell Lung Cancer.
Virtual Journal Club: Front-Line Therapy and Beyond Recent Perspectives on ALK-Positive Non-Small Cell Lung Cancer Reference Slides ALK Rearrangement in NSCLC ALK (anaplastic lymphoma kinase) is a receptor
More informationRob Ross, MD. Infinity Pharmaceuticals March 9 th, 2011
Heat Shock Protein 90 (Hsp90) Inhibition as a Potential Novel Approach to the Treatment of Patients with ALK Mutated Non-small Cell Lung Cancer (NSCLC) Rob Ross, MD Infinity Pharmaceuticals March 9 th,
More informationJoachim Aerts Erasmus MC Rotterdam, Netherlands. Drawing the map: molecular characterization of NSCLC
Joachim Aerts Erasmus MC Rotterdam, Netherlands Drawing the map: molecular characterization of NSCLC Disclosures Honoraria for advisory board/consultancy/speakers fee Eli Lilly Roche Boehringer Ingelheim
More informationASCO Highlights and Controversies in advanced Lung Cancer. Torino, 11 giugno 2015
ASCO 2015 Highlights and Controversies in advanced Lung Cancer Torino, 11 giugno 2015 Paolo Bironzo AOU S Luigi Gonzaga - Orbassano Scuola di Specializzazione in Oncologia Medica Università di Torino What
More informationDrug Resistance in ALK- and ROS1-Rearranged Lung Cancers. Alice T. Shaw, MD PhD Director, Center for Thoracic Cancers September 16, 2017
Drug Resistance in ALK- and ROS1-Rearranged Lung Cancers Alice T. Shaw, MD PhD Director, Center for Thoracic Cancers September 16, 2017 ALK and ROS1 are Related Tyrosine Kinases, and Both are Targeted
More informationHOW TO GET THE MOST INFORMATION FROM A TUMOR BIOPSY
HOW TO GET THE MOST INFORMATION FROM A TUMOR BIOPSY 7 TH Annual New York Lung Cancer Symposium Saturday, November 10, 2012 William D. Travis, M.D. Attending Thoracic Pathologist Memorial Sloan Kettering
More informationIndividualized therapy in lung cancer Where are we in 2012?
UNIVERSITY OF OF TORINO DEPARTMENT OF ONCOLOGY Individualized therapy in lung cancer Where are we in 2012? Giorgio V. Scagliotti University of Torino Professor of Medical Oncology Department of Oncology
More informationEGFR inhibitors in NSCLC
Suresh S. Ramalingam, MD Associate Professor Director of Medical Oncology Emory University i Winship Cancer Institute EGFR inhibitors in NSCLC Role in 2nd/3 rd line setting Role in first-line and maintenance
More informationManagement Guidelines and Targeted Therapies in Metastatic Non-Small Cell Lung Cancer: An Oncologist s Perspective
Management Guidelines and Targeted Therapies in Metastatic Non-Small Cell Lung Cancer: An Oncologist s Perspective Julie R. Brahmer, M.D. Associate Professor of Oncology The Sidney Kimmel Comprehensive
More informationNovel treatments for SCC Andrés Felipe Cardona, MD MS PhD.
Novel treatments for SCC Andrés Felipe Cardona, MD MS PhD. Clinical and Transla,onal Oncology Group Ins,tute of Oncology, Fundación Santa fe de Bogotá Clinical Epidemiology Cochrane Colombian Branch /
More informationInhibidores de EGFR Noemi Reguart, MD, PhD Hospital Clínic Barcelona IDIPAPS
Inhibidores de EGFR Noemi Reguart, MD, PhD Hospital Clínic Barcelona IDIPAPS Driver Mutations to Classify Lung Cancer Unknown 36% KRAS 25% EGFR 15% ALK 4% HER2 2% Double Mut 2% BRAF 2% PIK3CA
More informationNext Generation Sequencing in Clinical Practice: Impact on Therapeutic Decision Making
Next Generation Sequencing in Clinical Practice: Impact on Therapeutic Decision Making November 20, 2014 Capturing Value in Next Generation Sequencing Symposium Douglas Johnson MD, MSCI Vanderbilt-Ingram
More informationPersonalised Healthcare (PHC) with Foundation Medicine (FMI) Fatma Elçin KINIKLI, FMI Turkey, Science Leader
Personalised Healthcare (PHC) with Foundation Medicine (FMI) Fatma Elçin KINIKLI, FMI Turkey, Science Leader Agenda PHC Approach Provides Better Patient Outcome FMI offers Comprehensive Genomic Profiling,
More informationMET as a novel treatment target- the story of the sleeping beauty. Balazs Halmos M.D. Montefiore Medical Center/Albert Einstein College of Medicine
MET as a novel treatment target- the story of the sleeping beauty Balazs Halmos M.D. Montefiore Medical Center/Albert Einstein College of Medicine MET as a novel treatment target MET as an oncogene MET
More information1.Basis of resistance 2.Mechanisms of resistance 3.How to overcome resistance. 13/10/2017 Sara Redaelli
Dott.ssa Sara Redaelli 13/10/2017 1.Basis of resistance 2.Mechanisms of resistance 3.How to overcome resistance Tumor Heterogeneity: Oncogenic Drivers in NSCLC The Promise of Genotype-Directed Therapy
More information1 st line chemotherapy and contribution of targeted agents in non-driver addicted NSCLC
1 st line chemotherapy and contribution of targeted agents in non-driver addicted NSCLC Dr Ross Soo, FRACP National University Cancer Institute, Singapore National University Health System Cancer Science
More informationI. Diagnosis of the cancer type in CUP
Latest Research: USA I. Diagnosis of the cancer type in CUP II. Outcomes of site-specific therapy of the cancer type in CUP a. Prospective clinical trial b. Retrospective clinical trials 1 Latest Research:
More informationCorporate Medical Policy
Corporate Medical Policy Molecular Analysis for Targeted Therapy for Non-Small Cell Lung File Name: Origination: Last CAP Review: Next CAP Review: Last Review: molecular_analysis_for_targeted_therapy_for_non_small_cell_lung_cancer
More informationALK Fusion Oncogenes in Lung Adenocarcinoma
ALK Fusion Oncogenes in Lung Adenocarcinoma Vincent A Miller, MD Associate Attending Physician, Thoracic Oncology Service Memorial Sloan-Kettering Cancer Center New York, New York The identification of
More informationExpanding Therapeutic Options for Cancer Patients with Comprehensive Profiling Alexander Drilon MD
Expanding Therapeutic Options for Cancer Patients with Comprehensive Profiling Alexander Drilon MD Clinical Director, Early Drug Development Service Memorial Sloan Kettering Cancer Center COI Disclosure
More informationNouvelles stratégies Prise en charge en cas d altération oncogénique
Nouvelles stratégies Prise en charge en cas d altération oncogénique David Planchard (MD, PhD) Department of Cancer Medicine Thoracic Unit Gustave Roussy Villejuif (France) Disclosure Slide Consultancy
More informationIntegration of Genomics Into Clinical Pathways. Precision Medicine and Decision Support
Integration of Genomics Into Clinical Pathways Precision Medicine and Decision Support Faculty Andrew Hertler, MD, FACP Chief Medical Officer New Century Health Andrew Hertler, MD, FACP is employed by
More informationPlotting the course: optimizing treatment strategies in patients with advanced adenocarcinoma
Pieter E. Postmus University of Liverpool Liverpool, UK Plotting the course: optimizing treatment strategies in patients with advanced adenocarcinoma Disclosures Advisor Bristol-Myers Squibb AstraZeneca
More informationChanging demographics of smoking and its effects during therapy
Changing demographics of smoking and its effects during therapy Egbert F. Smit MD PhD. Dept. Pulmonary Diseases, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands Smoking prevalence adults
More informationBeyond ALK and EGFR: Novel Molecularly Driven Targeted Therapies in NSCLC
Beyond ALK and EGFR: Novel Molecularly Driven Targeted Therapies in NSCLC Simon Ekman, MD, PhD Senior Consultant in Oncology, Associate Professor Dept. of Oncology Karolinska University Hospital Stockholm,
More informationD Ross Camidge, MD, PhD
i n t e r v i e w D Ross Camidge, MD, PhD Dr Camidge is Director of the Thoracic Oncology Clinical Program and Associate Director for Clinical Research at the University of Colorado Cancer Center in Aurora,
More informationSlide 1. Slide 2. Slide 3. Individualized Therapy in Lung Cancer : Where are we in 2011? Notable Advances in Cancer Research in the last 2 years
Slide 1 Individualized Therapy in Lung Cancer : Where are we in 2011? Giorgio V. Scagliotti University of Torino Department of Clinical & Biological Sciences giorgio.scagliotti@unito.it Slide 2 Notable
More informationDo You Think Like the Experts? Refining the Management of Advanced NSCLC With ALK Rearrangement. Reference Slides Introduction
Do You Think Like the Experts? Refining the Management of Advanced NSCLC With ALK Rearrangement Reference Slides Introduction EML4-ALK Fusion Oncogene Key Driver in 3% to 7% NSCLC Inversion or Translocation
More informationSupplementary Online Content
Supplementary Online Content Kris MG, Johnson BE, Berry LD, et al. Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs. JAMA. doi:10.1001/jama.2014.3741 etable 1. Trials
More informationDiscovery of Essential Growth Drivers in Cancer Brings Magical Drugs to Patients
Discovery of Essential Growth Drivers in Cancer Brings Magical Drugs to Patients Hiroyuki Mano, MD, PhD Department of Cellular Signaling, Graduate School of Medicine, The University of Tokyo, Japan What
More informationLung Cancer Biomarkers: A Practical Update
Lung Cancer Biomarkers: A Practical Update Lynette M. Sholl, M.D. Associate Pathologist, Brigham and Women s Hospital Associate Professor, Harvard Medical School Boston, MA Disclosures Consultant for Foghorn
More informationOther Driver Mutations: cmet, B-RAF, RET, NTRK
Other Driver Mutations: cmet, B-RAF, RET, NTRK Luis E. Raez MD FACP FCCP Chief of Hematology/Oncology and Medical Director, Memorial Cancer Institute Clinical Professor of Medicine Herbert Wertheim College
More informationAliccia Bollig-Fischer, PhD Department of Oncology, Wayne State University Associate Director Genomics Core Molecular Therapeutics Program Karmanos
Aliccia Bollig-Fischer, PhD Department of Oncology, Wayne State University Associate Director Genomics Core Molecular Therapeutics Program Karmanos Cancer Institute Development of a multiplexed assay to
More informationMANEJO ACTUAL DEL PACIENTE CON CPNM CON REORDENACIONES ALK/ROS O MUTACIONES EN EGFR Rosario García Campelo Complejo Hospitalario Universitario A
MANEJO ACTUAL DEL PACIENTE CON CPNM CON REORDENACIONES ALK/ROS O MUTACIONES EN EGFR Rosario García Campelo Complejo Hospitalario Universitario A Coruña The seventies IMAGINE The eighties The Ninety 2000
More informationDisclosure of Relevant Financial Relationships NON-SMALL CELL LUNG CANCER: 70% PRESENT IN ADVANCED STAGE
MORPHOLOGY AND MOLECULAR TESTING IN NON-SMALL CELL OF LUNG NEW FRONTIEIRS IN CYTOPATHOLOGY PRACTICE American Society for Cytopathology San Antonio, Texas Sunday March 5, 2017 Disclosure of Relevant Financial
More informationNSCLC: Terapia medica nella fase avanzata. Paolo Bidoli S.C. Oncologia Medica H S. Gerardo Monza
NSCLC: Terapia medica nella fase avanzata Paolo Bidoli S.C. Oncologia Medica H S. Gerardo Monza First-line Second-line Third-line Not approved CT AND SILENT APPROVAL Docetaxel 1999 Paclitaxel Gemcitabine
More informationPIK3CA mutations are found in approximately 7% of
Original Article Impact of Concurrent PIK3CA Mutations on Response to EGFR Tyrosine Kinase Inhibition in EGFR-Mutant Lung Cancers and on Prognosis in Oncogene-Driven Lung Adenocarcinomas Juliana Eng, MD,*
More informationEvolution of Pathology
1 Traditional pathology Molecular pathology 2 Evolution of Pathology Gross Pathology Cellular Pathology Morphologic Pathology Molecular/Predictive Pathology Antonio Benivieni (1443-1502): First autopsy
More informationSequencing of therapies in mrcc. Ari Hakimi MD Assistant Professor Urology Service, Department of Surgery MSKCC
Sequencing of therapies in mrcc Ari Hakimi MD Assistant Professor Urology Service, Department of Surgery MSKCC Old Paradigm Sequencing approved agents VEGF TKI Sunitinib Pazopanib Axitinib TKI TKI MTORi
More informationCURRENT STANDARD OF CARE OF LUNG CANCER. Maroun El-Khoury, MD Consultant Oncologist/Hematologist American Hospital Dubai President of Medical staff
CURRENT STANDARD OF CARE OF LUNG CANCER Maroun El-Khoury, MD Consultant Oncologist/Hematologist American Hospital Dubai President of Medical staff Biopsy: Establish Diagnosis, Determine Histologic Subtype,
More informationTargeted therapy in NSCLC: do we progress? Prof. Dr. V. Surmont. Masterclass 27 september 2018
Targeted therapy in NSCLC: do we progress? Prof. Dr. V. Surmont Masterclass 27 september 2018 Outline Introduction EGFR TKI ALK TKI TKI for uncommon driver mutations Take home messages The promise of
More informationGiorgio V. Scagliotti Università di Torino Dipartimento di Oncologia
Giorgio V. Scagliotti Università di Torino Dipartimento di Oncologia giorgio.scagliotti@unito.it Politi K & Herbst R. Clin. Cancer Res. 2015; 21:2213 Breast Colorectal Gastric/GE Junction Tumor Type Head
More informationDr. Andres Wiernik. Lung Cancer
Dr. Andres Wiernik Lung Cancer Lung Cancer Facts - Demographics World Incidence: 1 8 million / year World Mortality: 1 6 million / year 5-year survival rates vary from 4 17% depending on stage and regional
More informationEGFR Mutation-Positive Acquired Resistance: Dominance of T790M
Treatment of EGFR Mutation-Positive Acquired Resistance: T790M+ or T790M- H. Jack West, MD Swedish Cancer Institute, Seattle, WA EGFR Mutation-Positive Acquired Resistance: Dominance of T790M Yu, Clin
More informationMolecular Diagnostic Pathology for Solid Tumor Oncology in the Era of Personalized Medicine
Molecular Diagnostic Pathology for Solid Tumor Oncology in the Era of Personalized Medicine George J. Netto MD Departments of Pathology, Urology and Oncology Johns Hopkins University Disclosures No Relevant
More informationPROGNOSTIC AND PREDICTIVE BIOMARKERS IN NSCLC. Federico Cappuzzo Istituto Toscano Tumori Ospedale Civile-Livorno Italy
PROGNOSTIC AND PREDICTIVE BIOMARKERS IN NSCLC Federico Cappuzzo Istituto Toscano Tumori Ospedale Civile-Livorno Italy Prognostic versus predictive Prognostic: In presence of the biomarker patient outcome
More informationTargeted Agents as Maintenance Therapy. Karen Kelly, MD Professor of Medicine UC Davis Cancer Center
Targeted Agents as Maintenance Therapy Karen Kelly, MD Professor of Medicine UC Davis Cancer Center Disclosures Genentech Advisory Board Maintenance Therapy Defined Treatment Non-Progressing Patients Drug
More informationIncorporating Immunotherapy into the treatment of NSCLC
Incorporating Immunotherapy into the treatment of NSCLC Suresh S. Ramalingam, MD Roberto C. Goizueta Chair for Cancer Research Assistant Dean for Cancer Research Deputy Director, Winship Cancer Institute
More informationLung Cancer Case. Since the patient was symptomatic, a targeted panel was sent. ALK FISH returned in 2 days and was positive.
Lung Cancer Case Jonathan Riess, M.D. M.S. Assistant Professor of Medicine University of California Davis School of Medicine UC Davis Comprehensive Cancer Center 63 year-old woman, never smoker, presents
More informationNSCLC 2 nd and further line therapies. Egbert F. Smit MD PhD. Dept. Thoracic Oncology, Netherlands Cancer Institute
NSCLC 2 nd and further line therapies Egbert F. Smit MD PhD. Dept. Thoracic Oncology, Netherlands Cancer Institute e.smit@nki.nl ESMO Guidelines 2016: Treatment of Stage IV nonsquamous NSCLC at progression
More informationTreatment of EGFR-Mutation+ NSCLC in 1st- and 2nd-Line
Treatment of EGFR-Mutation+ NSCLC in 1st- and 2nd-Line Martin Reck David F. Heigener Department of Thoracic Oncology Hospital Grosshansdorf Germany Identification of driver mutation in tumor specimens
More informationSuccesses and Challenges in Treating Squamous Cell Carcinoma of the Lung
Successes and Challenges in Treating Squamous Cell Carcinoma of the Lung Noemi Reguart,MD, PhD Hospital Clinic de Barcelona Barcelona, Spain SC-CRP-02660 Conversations in Oncology 2018 is a standalone
More informationNew options for old and new targets in NSCLC Rosario García Campelo Medical Oncology Unit University Hospital A Coruña
New options for old and new targets in NSCLC Rosario García Campelo Medical Oncology Unit University Hospital A Coruña Phase II GOAL TRIAL DESIGN Key inclusion criteria Patients with locally advanced or
More informationMaintenance therapy in advanced non-small cell lung cancer. Egbert F. Smit MD PhD Dept Thoracic Oncology Netherlands Cancer Institute
Maintenance therapy in advanced non-small cell lung cancer. Egbert F. Smit MD PhD Dept Thoracic Oncology Netherlands Cancer Institute e.smit@nki.nl Evolution of front line therapy in NSCLC unselected pts
More informationTake home message. Emilio Bria. II SESSIONE: Immunoterapia nel tumore del polmone
II SESSIONE: Immunoterapia nel tumore del polmone Take home message Emilio Bria Oncologia, Dipart. di Medicina, Università di Verona, Az. Osp. Univ. Int., Verona emilio.bria@univr.it Roma, 28 Marzo 2017
More informationLung Cancer. Karen Reckamp, MD Medical Director, Clinical Research. Click to edit Master Presentation Date
Advances in Targeted Therapy for Lung Cancer Karen Reckamp, MD Medical Director, Clinical Research City of Hope Comprehensive Cancer Center Click to edit Master Presentation Date Disclosures Consultant
More informationLeading the Way to Precision Care: Molecular Diagnostics and Therapeutics in Lung Cancers. Mark G Kris, MD Memorial Sloan Kettering New Amsterdam USA
Leading the Way to Precision Care: Molecular Diagnostics and Therapeutics in Lung Cancers Mark G Kris, MD Memorial Sloan Kettering New Amsterdam USA Molecular Therapeutics in Lung Cancers Financial Disclosures
More informationClinical Biomarker in Kidney Cancer. Maria Nirvana Formiga, M.D., Ph.D.
Clinical Biomarker in Kidney Cancer Maria Nirvana Formiga, M.D., Ph.D. Disclosures I am on the Speaker s Bureau with Pfizer and Bayer Clinical trials of BMS and Pfizer Kidney Cancer 70% new cases in developed
More informationMECHANISMS OF 1ST GENERATION RESISTANCE. Byoung Chul Cho, M.D., Ph.D.
MECHANISMS OF 1ST GENERATION RESISTANCE Byoung Chul Cho, M.D., Ph.D. CONFLICT OF INTEREST Research funding: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST Consulting role: Novartis, AstraZeneca,
More informationMET skipping mutation, EGFR
New NSCLC biomarkers in clinical research: detection of MET skipping mutation, EGFR T790M, and other important biomarkers Fernando López-Ríos Laboratorio de Dianas Terapéuticas Hospital Universitario HM
More informationDM Seminar. ALK gene rearrangements & ALK targeted therapy in NSCLC Dr Sarat
DM Seminar ALK gene rearrangements & ALK targeted therapy in NSCLC Dr Sarat Introduction Discovery of activating mutations in kinase domain of epidermal growth factor receptor (EGFR) opened a new era of
More informationBiomarkers of Response to EGFR-TKIs EORTC-NCI-ASCO Meeting on Molecular Markers in Cancer November 17, 2007
Biomarkers of Response to EGFR-TKIs EORTC-NCI-ASCO Meeting on Molecular Markers in Cancer November 17, 2007 Bruce E. Johnson, MD Dana-Farber Cancer Institute, Brigham and Women s Hospital, and Harvard
More informationTargeted therapy in lung cancer : experience of NIO-RABAT
Targeted therapy in lung cancer : experience of NIO-RABAT I.ELGHISSASSI, H.ERRIHANI Medical oncology department, NIO- RABAT 02-05- 2012, FEZ In Morocco, lung cancer is the most common tumor among men At
More informationTargeted/Immunotherapy & Molecular Profiling State-of-the-art in Cancer Care
Targeted/Immunotherapy & Molecular Profiling State-of-the-art in Cancer Care Manmeet Ahluwalia, MD, FACP Miller Family Endowed Chair in Neuro-Oncology Director Brain Metastasis Research Program Cleveland
More informationLung Cancer Update 2016 BAONS Oncology Care Update
Lung Cancer Update 2016 BAONS Oncology Care Update Matthew Gubens, MD, MS Assistant Professor Chair, Thoracic Oncology Site Committee UCSF Helen Diller Family Comprehensive Cancer Center Disclosures Consulting
More informationPage: 1 of 27. Molecular Analysis for Targeted Therapy of Non-Small-Cell Lung Cancer
Last Review Status/Date: December 2014 Page: 1 of 27 Non-Small-Cell Lung Cancer Description Over half of patients with non-small-cell lung cancer (NSCLC) present with advanced and therefore incurable disease,
More informationLihong Ma 1 *, Zhengbo Song 2 *, Yong Song 1, Yiping Zhang 2. Original Article
Original Article MET overexpression coexisting with epidermal growth factor receptor mutation influence clinical efficacy of EGFR-tyrosine kinase inhibitors in lung adenocarcinoma patients Lihong Ma 1
More informationPersonalized Genetics
Personalized Genetics Understanding Your Genetic Test Results Tracey Evans, MD September 29, 2017 Genetics 101 Punnett Square Genetic Pedigree 2 Genetics 101 Punnett Square Genetic Pedigree 3 It s not
More informationTargeted Therapy for NSCLC: EGFR and ALK Fadlo R. Khuri, MD
EGFR and ALK Fadlo R. Khuri, MD President, American University of Beirut Professor of Medicine July 26, 2018 A great year end! Targeted Therapy for NSCLC: Evolving Landscape of Lung Adenocarcinoma NSCLC
More informationTargeted therapies in NSCLC beyond EGFR and ALK
Targeted therapies in NSCLC beyond EGFR and ALK David Planchard (MD, PhD) Department of Cancer Medicine Thoracic Unit Gustave Roussy Villejuif (France) Great advances have been made in lung cancer therapy:
More informationPractice changing studies in lung cancer 2017
1 Practice changing studies in lung cancer 2017 Rolf Stahel University Hospital of Zürich Cape Town, February 16, 2018 DISCLOSURE OF INTEREST Consultant or Advisory Role in the last two years I have received
More informationHacia una mayor individualización clínica en el CPNM. J.M. Sánchez Torres H.U. Princesa, Madrid
Hacia una mayor individualización clínica en el CPNM J.M. Sánchez Torres H.U. Princesa, Madrid Lung cancer histologic subtypes NSCLC (80-85%) SCLC (15-20%) Squamous carcinoma (25 30%) Non-squamous carcinoma
More informationManagement Strategies for Lung Cancer Sensitive or Resistant to EGRF Inhibitors
Management Strategies for Lung Cancer Sensitive or Resistant to EGRF Inhibitors Conor E. Steuer, MD Assistant Professor The Winship Cancer Institute of Emory University July 27, 2017 1 Lung Cancer One
More informationTargeted Therapy In ALK Rearranged Advanced/Metastatic Non Small Cell Lung Cancer (NSCLC)
Targeted Therapy In ALK Rearranged Advanced/Metastatic Non Small Cell Lung Cancer (NSCLC) NASR M. A. ALLAHLOUBI PROFESSOR OF MEDICAL ONCOLOGY NCI, CAIRO UNIVERSITY Bridging Gaps in Oncology, Thursday 28
More informationASSOCIAZIONE CULTURALE GIUSEPPE DOSSETTI THE PARADIGM OF PERSONALIZED THERAPY IN ONCOLOGY
ASSOCIAZIONE CULTURALE GIUSEPPE DOSSETTI THE PARADIGM OF PERSONALIZED THERAPY IN ONCOLOGY Giampietro Gasparini Oncology - San Filippo Neri Hospital Rome, Italy Roma, 26 October 2011 www.professorgasparini.com
More informationThe Role of Pathology/Molecular Diagnostic in Personalized Medicine
The Role of Pathology/Molecular Diagnostic in Personalized Medicine Ignacio I. Wistuba, M.D. Jay and Lori Eissenberg Professor in Lung Cancer Director of the Thoracic Molecular Pathology Lab Departments
More informationProteomic Testing for Targeted Therapy in Non-Small-Cell Lung Cancer
Last Review Status/Date: December 2015 Page: 1 of 21 Small-Cell Lung Cancer Summary Proteomic testing has been proposed as a way to predict outcomes and response to and selection of targeted therapy for
More informationReviewers' comments: Reviewer #1 (Remarks to the Author):
Reviewers' comments: Reviewer #1 (Remarks to the Author): The authors have presented data demonstrating activation of AKT as a common resistance mechanism in EGFR mutation positive, EGFR TKI resistant
More informationMolecular Pathology and Lung Cancer. A. John Iafrate MD-PhD Department of Pathology Massachusetts General Hospital Boston, MA
Molecular Pathology and Lung Cancer A. John Iafrate MD-PhD Department of Pathology Massachusetts General Hospital Boston, MA aiafrate@partners.org Disclosures Preliminary patent application NGS AMP Fusion
More informationOptimum Sequencing of EGFR targeted therapy in NSCLC. Dr. Sema SEZGİN GÖKSU Akdeniz Univercity, Antalya, Turkey
Optimum Sequencing of EGFR targeted therapy in NSCLC Dr. Sema SEZGİN GÖKSU Akdeniz Univercity, Antalya, Turkey Lung cancer NSCLC SCLC adeno squamous EGFR ALK ROS1 BRAF HER2 KRAS EGFR Transl Lung Cancer
More informationSolange Peters, MD-PhD Cancer Center, Lausanne Switzerland EGFR AND NSCLC
Solange Peters, MD-PhD Cancer Center, Lausanne Switzerland EGFR AND NSCLC Interactive Clinical Case History Maria José 1963 Since end 2010, progressive dyspnea Attends Emergency Room 02.01.2011 after 3
More informationStratégies thérapeutiques optimales en cas de positivité HER2, BRAF, ALK
Stratégies thérapeutiques optimales en cas de positivité HER2, BRAF, ALK David Planchard (MD, PhD) Department of Cancer Medicine Thoracic Unit Gustave Roussy Villejuif (France) Disclosure Slide AstraZeneca,
More informationCLINICAL MEDICAL POLICY
Policy Name: Policy Number: Responsible Department(s): CLINICAL MEDICAL POLICY Molecular Tumor Markers for Non-Small Cell Lung Cancer (NSCLC) MP-061-MD-DE Medical Management Provider Notice Date: 10/15/2018;
More informationHeat shock proteins as an emerging therapeutic target
UNIVERSITY OF OF TORINO DEPARTMENT OF ONCOLOGY Heat shock proteins as an emerging therapeutic target Giorgio V. Scagliotti University of Torino Professor of Medical Oncology Department of Oncology giorgio.scagliotti@unito.it
More informationDesign considerations for Phase II trials incorporating biomarkers
Design considerations for Phase II trials incorporating biomarkers Sumithra J. Mandrekar Professor of Biostatistics, Mayo Clinic Pre-Meeting Workshop Enhancing the Design and Conduct of Phase II Studies
More information