Individualized therapy in lung cancer Where are we in 2012?
|
|
- Gilbert Skinner
- 5 years ago
- Views:
Transcription
1 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
2 UNIVERSITY OF OF TORINO DEPARTMENT OF ONCOLOGY Cancer Research at the roundabout 1. Cancer is a genetic somatic disease (5% inherited) 2. (Very likely) originates from stem cells 3. It is caused by genetic alterations of a handful of genes (Oncogenes or Driver genes ) 4. It is often possible to identify these genetic lesions by molecular diagnosis 5. Targeted Therapy is only effective when aimed at the alteration of the driver gene(s): Oncogenic Addiction
3 Chipping away at the lung cancer genome Lung Adenocarcinoma Squamous Cell Carcinoma of the lung Pao W. Nat. Med ; Sos M. and Thomas R. Oncogene 2012
4 Changes in the therapeutic landscape of stage IV lung cancer
5 Changes in the therapeutic landscape of stage IV lung cancer Adeno LCC/NOS SCC SCLC
6 Changes in the therapeutic landscape of stage IV lung cancer Chemotherapy and PCI Adeno LCC/NOS SCC SCLC
7 Changes in the therapeutic landscape of stage IV lung cancer HER2 EGFR mutants ALK ROS/RET b-raf K-ras K-ras Chemotherapy and PCI Adeno LCC/NOS SCC SCLC
8 EGFR-TKIs and EGFR Mutation -Directed Front - Line Studies Study Entry Criteria HR for PFS (EGFR mut +) IPASS Mok NEJM 2009 First SIGNAL Proc. IASLC 2009 NEJ002 NEJM 2010 Proc. ASCO 2011 WJTOG3405 Lancet Onc Asiatic, never- & light smokers, adenocarcinoma (EGFR mut %) Adenocarcinoma, Neversmokers (EGFR mut + 44%) 0.48 ( ) 0.61 ( ) EGFR Mutation + (all) 0.35 ( ) EGFR Mutation + (all) ( ) HR for OS (EGFR mut +) 0.91 * ( ) *overall population 0.82 ( ) ( ) ( ) EURTAC (EU) EGFR Mutation + (all) 0.42 ( )? OPTIMAL (China) EGFR Mutation + (all) 0.16 ( ) 1.04 ( ) LUX-LUNG 3 EGFR Mutation + (all) 0.58 ( )?
9 % Decrease or increase from baseline Tumour responses to crizotinib by patient A ORR 61% N= PROFILE 1005 ORR 51% N= best objective response according to RECIST: Progressive disease Stable disease Partial response Complete response 1 Camidge R, et al. Progression-Free Survival (PFS) from a Phase 1 Study of Crizotinib (PF ) in Patients with ALK-Positive Non-Small Cell Lung Cancer (NSCLC). Presented at ASCO 2011; Abstract Kim DW, et al. A Global Phase 2 Study Including Efficacy, Safety, and Patient-reported Outcomes with Crizotinib in Patients with ALK-positive Non-small Cell Lung Cancer. Presented at ECCO/ESMO 2011; Abstract 9084
10 Decrease or Increase From Baseline (%) Crizotinib and Tumor Responses in Patients with Advanced ROS1+ NSCLC (N=14*) Response Rate 57% PD SD PR CR *Response-evaluable population. Tumor ROS1 FISH-positive, but negative for ROS1 fusion gene expression. Crizotinib held for >6 wks prior to first scans which showed PD. Shaw A. et al. Proc. ASCO 2012
11
12 Erlotinib in EGFR mutant NSCLC Vemurafenib in BRAF mutant melanomas Crizotinib in ALK rearranged NSCLC
13 Kinase oncogene dependence and principles of drug resistance Wagle N. et al. J. Clin. Oncol. 2011; 29:3085
14 Genotypic Evolution of Lung Cancer Acquiring Resistance to EGFR and ALK Inhibitors A L K A L K E G F R A L K K R A S A L K A L K Sequist L. et al. Sci. Transl. Med. 2011; 3 (75) 75ra26 Doebele R. et al. Proc. ASCO 2012
15 How to improve results in EGFR mutants? Chemo-naïve advanced NSCLC EGFR mutant EGFR TKI + HD 2 nd -gen EGFR TKI EGFR TKI + BCL-2i EGFR TKI + IGF-1Ri EGFR TKI + METi EGFR TKI + HCQ EGFR TKI (diff dosing schedules) EGFR TKI + chemo EGFR mutant NSCLC with acquired resistance* Potent 2 nd -gen EGFR TKI 2 nd -gen EGFR TKI + cetuximab Chemo EGFR TKI 2 nd -gen EGFR TKI + METi
16 Many new drugs for use post-crizotinib in development + HSP90 inhibitors, + pemetrexed based regimens Weickhardt and Camidge, Clin Invest 2011
17 Mechanisms of Acquired Resistance to BRAF Inhibitors [1] [2] NRAS Q61 COT CRAF BRAF inhibitor BRAF V600E [3,4] PDGFRβ or IGF1R or EGFR PI3K PI3Ki or AKTi AKT [4,6,9-11] MEK-dependent progression 1. Nazarian R, et al. Nature Johannessen CM, et al. Nature Poulikakos, et al. Nature Shi H, et al. Cancer Discov Wagle N, et al. J Clin Oncol P P MEK MEKi ERK Survival [5] MEK-independent progression [1,6-8] 6. Villanueva J, et al. Cancer Cell Prahallad A, et al. Nature Corcoran RB, et al. Cancer Discov Jiang CC, et al. Clin Cancer Res Atefi M, et al. PLoS One Su F, et al. Cancer Res
18 Monitoring for resistance in CRC Misale S. et al. Nature 2012; 486 : 532 Diaz LA, Jr. et al. Nature 2012; 486 : 537
19 K-ras mutation & NSCLC Is k-ras mutation prognostic or predictive? Is there any evidence for excluding k-ras mutants from receiving chemo? K-ras K-ras K-ras mutation not predictive or prognostic in resected early stage NSCLC treated with adjuvant chemotherapy (Shepherd F. et al. Proc. ASCO 2012) Meta-Analysis of 881 Cases - Stages I-IV - RR of 2.35 ( ) at 2 years k-ras mutation may be associated with shortened survival but need to be confirmed in well designed multivariate analyses addjusted for known prognostic factors (Huncharek M et al., Carcinogenesis 1999) K-RAS mutational status does not predict benefit from the anti-egfr monoclonal antibody cetuximab (O Byrne Lancet Oncology 2011)
20 Changes in the therapeutic landscape of stage IV lung cancer DDR2 mutation 0% KRAS mutation 2% Unknown 37% PIK3CA mutation 8% PTEN loss, complete 11% FGFR1 amplification 25% PTEN mutation 17% Target N Frequency 95% CI FGFR1 amplification 13/52 25% 15 38% PTEN mutation 3/18 17% 5 37% PTEN loss, complete 3/27 11% 3 26% PIK3CA mutation 4/52 8% 2 17% KRAS mutation 1/52 2% 1 9% DDR2 mutation 0/18 0% 0 15% SCC Paik et al. J Clin Oncol 30: 2012 (suppl; abstr 7505)
21 Therapeutic targets in squamous cell lung carcinoma Gene Event type Frequency CDKN2A Deletion/mutation/methylation 72 PI3KCA Mutation 16 PTEN Mutation/Detection 15 FGFR1 Amplification 15 EGFR Amplification 9 PDGFRA Amplification/Mutation 9 CCND1 Amplification 8 DDR2 Mutation 4 BRAF Mutation 4 ERBB2 Amplification 4 FGFR2 Mutation 3 Govindan et al. J Clin Oncol 30, 2012 (suppl; abstr 7006)
22 FGFR1 amplification in squamous cell lung carcinoma Abstract No of cases Histology subtype Disease stage(s) Technique Definition of amplification Squamous I IV FISH Median of 6 or more gene copies Squamous I IV FISH Mean of 6 or more gene copies Squamous I IV Quantitative PCR Predicted CNV of 2 in 1 exon Squamous I IV FISH Copy number >2 and <9 (low); >9 (high) % amplified % polysomy (if available) / CNV, copy number variation Martinez Marti et al. J Clin Oncol 30, 2012 (suppl; abstr 7041) Toschi et al. J Clin Oncol 30, 2012 (suppl; abstr 7061) Cote et al. J Clin Oncol 30, 2012 (suppl; abstr 7063) Wei et al. J Clin Oncol 30, 2012 (suppl; abstr 7545)
23 Therapeutic targets in squamous cell lung carcinoma Gene Event type Frequency CDKN2A Deletion/mutation/methylation 72 PI3KCA Mutation 16 PTEN Mutation/Detection 15 FGFR1 Amplification 15 EGFR Amplification 9 PDGFRA Amplification/Mutation 9 CCND1 Amplification 8 DDR2 Mutation 4 BRAF Mutation 4 ERBB2 Amplification 4 FGFR2 Mutation 3 Govindan et al. J Clin Oncol 30, 2012 (suppl; abstr 7006)
24 Changes in the therapeutic landscape of stage IV lung cancer Histology still guide the therapeutic choice for the vast majority of our patients K-ras K-ras Adeno LCC/NOS SCC
25 Updated Treatment Algorithm for Advanced-Stage NSCLC (2012) Proposed Treatment Algorithm EGFR Mutation Positive or ALK Positive Molecular Good PS Clinical (PS) Poor PS Erlotinib or Crizotinib Non-squamous Histologic Squamous Single-Agent Chemotherapy Bevacizumab Eligible Bevacizumab Ineligible Platinum/Pemetrexed (or Other*) ± Bevacizumab Clinical Platinum/Pemetrexed (or Other*) Platinum/Gemcitabine (or Other*) Firstline Progression Bevacizumab, Erlotinib, Pemetrexed or Observation End of First-line Chemotherapy Erlotinib or Pemetrexed or Observation Erlotinib or Observation Based on Prior Therapy Maintenance Chemotherapy by Algorithm Based on Prior Therapy Based on Prior Therapy Based on Prior Therapy Secondline *Other docetaxel, paclitaxel, vinorelbine Gandara, Mack, Li, Lara, Herbst. Clin Lung Cancer, 2009
26 Cis/Pem vs. Cis/Gem in Advanced NSCLC Scagliotti GV et al. J. Clin. Oncol 2008; 26:3543
27 Relative expre. levels Relative expre. levels Squamous cell carcinoma of the lung compared with other histotypes shows higher messenger RNA and protein levels for thymidylate synthase p< P<0.001 Adenocarcinoma Squamous P<0.001 Ceppi et al. Cancer 2006
28 TS in Lung Cancer : a Japanese Large-Scale Study 2621 Japanese lung cancer patients Laser capture microdissected sections cut from primary tumors, surrounding normal lung tissues and involved nodes Tanaka F. et al. Ann. Oncol Feb. 14 ahead of print
29 Summary of the Effect of Pemetrexed in Patients with Advanced NSCLC by ALK Status Reports from three small, retrospective analyses suggest pemetrexed given as a single agent or in combination with chemotherapy may be effective in ALK-positive NSCLC 1 3 Report Camidge et al 2 Lee et al 3 Treatment Pemetrexed single agent or combination therapy, any line Second-line or later single-agent pemetrexed Study populations and comparator populations N ORR (%) Time to event, months (95% CI) ALK-positive NSCLC PFS, 9.0 (95% CI: 3 12) ALK/EGFR/KRAS-triple negative NSCLC Altavilla et al 1 Pemtrexed + cisplatin ALK-positive NSCLC, adenocarcinoma PFS, 4.0 (95% CI: 3 5) ALK-positive NSCLC TTP, 9.2 (95% CI: ) EGFR wild-type NSCLC 37 TTP, TTP, 9.0 ALK-negative NSCLC 32 TTP, 6.2 TTP, time to progression 1. Altavilla G, Santarpia M, Arrigo C, et al. J Clin Oncol 2010;28 (Abstract 7610) 2. Camidge DR, Kono SA, Lu X, et al. J Thorac Oncol 2011;6: Lee JO, Kim TM, Lee SH, et al. J Thorac Oncol 2011;6:
30 All ALK-neg TS2 TS Expression in ALK+ versus ALK- NSCLC TS Expression N Median 95% CI Range p Value ALK+ Patients ALK- Patients < TS in patients with ALK+ cancers 0 TS in patients with ALK- cancers Gandara D. et al. Proc. ASCO 2012
31 Biomarkers & outcome in the Norwegian Study Carbo/Pem vs. Carbo/Gem Grønberg B. et al. Proc. ASCO 2011
32 ITACA Adjuvant Trial Pharmacogenomics: Yes or No? Taxanes High Profile 4 Control ERCC1 High TS Low High Profile 3 Profile 2 Pem Control Cis/Gem Low TS Control Cis/Pem Low Profile 1 Control Control = investigators choice of cisplatin-based doublet Primary endpoint = OS; Sample size = 700 patients
33 Phase II Study of Preoperative Cis/Pem in Stage IIIa N2 non-squamous NSCLC N=33 Stage IIIa N2 by Med (+CT Scan + PET) Cis 75 mg/ m2 & Pem 500 mg/m2 x 3 q3wks Restaging by CT scan and PET Surgery Biomarker Assessment TS, TTF-1, E2F1, ERCC1, BRCA1 (Functional Imaging Changes) Primary end point : ORR Secondary end points :pcr,pfs,os, tumor downstaging, toxicity
34 EPIC Trial Elderly Patients Individualized Chemotherapy Trial 2:1 Randomization Individualized Arm Control Arm EGFR Mut + Squamous Cell Carcinoma Treatment based on Investigators Preference Yes Yes No EGFR Mut + Off Study Yes ERCC1 low RRM1 high ERCC1 high RRM1 low ERCC1 low RRM1 low ERCC1 high RRM1 high No Carboplatin Gemcitabine Carbo/Gem Taxane ERCC1 low TS high ERCC1 high TS low ERCC1 low TS low ERCC1 high TS high Carboplatin Pemetrexed Carbo/Pem RRM1 low RRM1 high PIs : G. Simon & G. Scagliotti University of South Carolina (Hollings Cancer Center) & University of Torino Gemcitabine Taxane
35 Conclusion (1) In 15-20% of NSCLC (mainly adenocarcinoma) a driver mutation may be detected and already druggable. Other mutations are detactable in adenocarcinoma and more than 60% of SCCs present with some genetic abnormality. A differential activity by histology has been consistently reported for pemetrexed and makes a platinum-pemetrexed doublet a reference combination for non-squamous NSCLC without driver mutations. TS is a good candidate pharmacogenomic marker for pemetrexed activity and this hypothesis is currently prospectively validated. The definition of homogeneous genetic subgroups of tumors and the search for individualized approaches is the way to substiantially increase survival expectancy in this disease.
36 Relevant Predictive Biomarkers and NSCLC Class Agent Biomarkers Robustness Cytotoxic drugs Cisplatin ERCC1 RRM1 BRCA1 Gemcitabine RRM Pemetrexed Paclitaxel FPGS TS MAPtau Beta-tubulin III Targeted therapies Erlotinib EGFR mutation FISH EGFR K-Ras wt RASSF1A / 9pLOH Bevacizumab Circulating VEGF
Slide 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 informationPrognostic and predictive biomarkers in
OLOGICAL SCIENCES O DEPT. OF CLINICAL & BIO UNIVERSITY UNIVERSTY OF TORINO Prognostic and predictive biomarkers in early stage NSCLC Giorgio V. Scagliotti University of Torino Department of Clinical &
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 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 informationSelection of systemic therapy in Advanced NSCLC based on biological factors. State of the Art
Selection of systemic therapy in Advanced NSCLC based on biological factors State of the Art Giorgio V. Scagliotti University of Torino Department of Clinical & Biological Sciences giorgio.scagliotti@unito.it
More informationMedical Oncology: State of the Art Therapy in Advanced NSCLC: 2011 looking toward 2015
Medical Oncology: State of the Art Therapy in Advanced NSCLC: 2011 looking toward 2015 David R. Gandara, MD University of California Davis Cancer Center Algorithm for Therapy of Advanced Stage NSCLC: 2009
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 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 information1st line chemotherapy and contribution of targeted agents
ESMO PRECEPTORSHIP PROGRAMME NON-SM ALL-CELL LUNG CANCER 1st line chemotherapy and contribution of targeted agents Yi-Long Wu Guangdong Lung Cancer Institute Guangdong General Hospital Guangdong Academy
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 informationTreatment of EGFR mutant advanced NSCLC
Treatment of EGFR mutant advanced NSCLC Raffaele Califano Department of Medical Oncology The Christie and Manchester University Hospital Manchester, UK Outline Data on first-line Overcoming T790M mutation
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 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 information11/21/2009. Erlotinib in KRAS Mt patients. Bevacizumab in Squamous patients
Decision-Making in Non-Small Cell Lung Cancer (NSCLC): Moving from Empiric to Personalized & Molecular-based Therapy David R. Gandara, MD University of California Davis Cancer Center Disclosures Research
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 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 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 informationHeather Wakelee, M.D.
Heather Wakelee, M.D. Assistant Professor of Medicine, Oncology Stanford University Sponsored by Educational Grant Support from Adjuvant (Post-Operative) Lung Cancer Chemotherapy Heather Wakelee, M.D.
More informationSystemic therapy in early stage NSCLC. Disclosures
Systemic therapy in early stage NSCLC Christian Manegold, MD Professor of Medicine, Heidelberg University Interdisciplinary Thoracic Oncology Department of Surgery University Medical Center Mannheim, Germany
More informationEGFR MUTATIONS: EGFR PATHWAY AND SELECTION OF FIRST-LINE THERAPY WITH TYROSINE KINASE INHIBITORS
EGFR MUTATIONS: EGFR PATHWAY AND SELECTION OF FIRST-LINE THERAPY WITH TYROSINE KINASE INHIBITORS Federico Cappuzzo Istituto Clinico Humanitas IRCCS Rozzano-Italy The EGFR/HER Family Ligand binding domain
More informationExploring Personalized Therapy for First Line Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)
Exploring Personalized Therapy for First Line Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC) Suresh S. Ramalingam, MD Director of Thoracic Oncology Associate Professor Emory University Atlanta,
More informationTreatment of EGFR mutant advanced NSCLC
Treatment of EGFR mutant advanced NSCLC Raffaele Califano Department of Medical Oncology The Christie and University Hospital of South Manchester, Manchester, UK Outline Data on first-line Overcoming T790M
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 informationMaintenance Therapy for Advanced NSCLC: When, What, Why & What s Left After Post-Maintenance Relapse?
Maintenance Therapy for Advanced NSCLC: When, What, Why & What s Left After Post-Maintenance Relapse? Mark A. Socinski, MD Professor of Medicine Multidisciplinary Thoracic Oncology Program Lineberger Comprehensive
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 informationPersonalized Medicine for Advanced NSCLC in East Asia
Personalized Medicine for Advanced NSCLC in East Asia - Update treatment strategy for NSCLC based on Japanese clinical practice guideline - Masahiro Tsuboi, M.D., Ph.D. Associate-professor, School of Medicine,
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 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 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 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 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 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 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 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 informationThe Evolving Role of Molecular Markers in Managing Non-Small Cell Lung Cancer
The Evolving Role of Molecular Markers in Managing Non-Small Cell Lung Cancer Nathan A. Pennell, M.D., Ph.D. Assistant Professor Solid Tumor Oncology Cleveland Clinic Taussig Cancer Institute www.cancergrace.org
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 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 informationMETASTATIC COLORECTAL CANCER: TUMOR MUTATIONAL ANALYSIS AND ITS IMPACT ON CHEMOTHERAPY SUMA SATTI, MD
METASTATIC COLORECTAL CANCER: TUMOR MUTATIONAL ANALYSIS AND ITS IMPACT ON CHEMOTHERAPY SUMA SATTI, MD INTRODUCTION Second leading cause of cancer related death in the United States. 136,830 cases in 2014
More informationALCHEMIST. Adjuvant Lung Cancer Enrichment Marker Identification And Sequencing Trials
ALCHEMIST Adjuvant Lung Cancer Enrichment Marker Identification And Sequencing Trials What is ALCHEMIST? ALCHEMIST is 3 integrated trials testing targeted therapy in early stage lung cancer: l A151216:
More informationHistology in the Decision-making Process
Histology in the Decision-making Process Giorgio V. Scagliotti University of Torino Department of Clinical & Biological Sciences giorgio.scagliotti@unito.it Lung Cancer Four Main Histological Subtypes
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 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 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 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 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 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 informationSystemic therapy for Non-Small Cell Lung Cancer in 2013 (What you should know)
Systemic therapy for Non-Small Cell Lung Cancer in 2013 (What you should know) นายแพทย ช ยย ทธ ย ทธ เจร ญธรรม หน วยมะเร งว ทยา ภาคว ชาอาย ร อาย รศาสตร Inter-hospitol Conference, 16 th March 2013 Systemic
More informationASCO Highlights Lung Cancer
ASCO Highlights Lung Cancer Anne S. Tsao, M.D. Director, Mesothelioma Program Assistant Professor July 11, 2009 The University of Texas MD ANDERSON CANCER CENTER Department of Thoracic/Head & Neck Medical
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 informationEstado actual del tratamiento neoadyuvante y adyuvante a la cirugía en estadios iniciales de cáncer de pulmón no microcítico
Estado actual del tratamiento neoadyuvante y adyuvante a la cirugía en estadios iniciales de cáncer de pulmón no microcítico Enriqueta Felip Vall d Hebron University Hospital Barcelona, Spain Stage I-II
More informationSlide 1. Slide 2 Maintenance Therapy Options. Slide 3. Maintenance Therapy in the Management of Non-Small Cell Lung Cancer. Maintenance Chemotherapy
Slide 1 Maintenance Therapy in the Management of Non-Small Cell Lung Cancer Frances A Shepherd, MD FRCPC Scott Taylor Chair in Lung Cancer Research Princess Margaret Hospital, Professor of Medicine, University
More informationFrequency of Epidermal Growth Factor Mutation Status and Its Effect on Outcome of Patients with Adenocarcinoma of the Lung
Journal of Cancer Therapy, 2014, 5, 1012-1020 Published Online September 2014 in SciRes. http://www.scirp.org/journal/jct http://dx.doi.org/10.4236/jct.2014.511106 Frequency of Epidermal Growth Factor
More informationTarget therapy nel NSCLC con EGFR M+ Cesare Gridelli Division of Medical Oncology S.G. Moscati Hospital Avellino (Italy)
Target therapy nel NSCLC con EGFR M+ Cesare Gridelli Division of Medical Oncology S.G. Moscati Hospital Avellino (Italy) cgridelli@libero.it First-Line Treatment of Advanced NSCLC EGFR-mutation analysis
More informationSequencing in EGFR-Mutated NSCLC: Does Order Matter?
Sequencing in EGFR-Mutated NSCLC: Does Order Matter? Maximilian J. Hochmair, MD Otto Wagner Hospital Vienna, Austria Disclosures Honoraria: AstraZeneca, AbbVie, Pfizer, Boehringer Ingelheim, Roche, MSD,
More informationAntiangiogenici in combinazione a chemioterapia in prima linea: bevacizumab
Micro-ambiente tumorale. Antiangiogenici e immunoterapia: miti e realtà Milano, 11 Ottobre 2016 Antiangiogenici in combinazione a chemioterapia in prima linea: bevacizumab Francesco Grossi U.O.S. Tumori
More informationMedical Treatment of Advanced Lung Cancer
Medical Treatment of Advanced Lung Cancer Oncology for Scientists April 26, 2018 Edwin Yau, MD., Ph.D. Assistant Professor of Oncology Department of Medicine Department of Cancer Genetics and Genomics
More informationOptimal Application of Adjuvant Therapy in NSCLC
Optimal Application of Adjuvant Therapy in NSCLC Heather Wakelee, MD Stanford University, Stanford Cancer Institute Post 1995 Meta-Analysis : NSCLC Randomized Adjuvant Platinum Trials Trial Stage n Chemo
More informationMAINTENANCE TREATMENT CHEMO MAINTENANCE OR TARGETED OF BOTH? Martin Reck Department of Thoracic Oncology LungenClinic Grosshansdorf
MAINTENANCE TREATMENT CHEMO MAINTENANCE OR TARGETED OF BOTH? Martin Reck Department of Thoracic Oncology LungenClinic Grosshansdorf OUTLINE Background and Concept Switch Maintenance Continuation Maintenance
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 informationSlide 1. Slide 2 Post 1995 Meta-Analysis : Slide 3
Slide 1 Optimal Application of Adjuvant Therapy in NSCLC Heather Wakelee, MD Stanford University, Stanford Cancer Institute Slide 2 Post 1995 Meta-Analysis : NSCLC Randomized Adjuvant Platinum Trials Trial
More informationRecent Advances in Lung Cancer: Updates from ASCO 2017
Recent Advances in Lung Cancer: Updates from ASCO 2017 Charu Aggarwal, MD, MPH Assistant Professor of Medicine Division of Hematology-Oncology Abramson Cancer Center University of Pennsylvania 6/15/2017
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 informationNew Options for Achieving Individualized Approaches to Non-Small Cell Lung Cancer (NSCLC) Management
New Options for Achieving Individualized Approaches to Non-Small Cell Lung Cancer (NSCLC) Management Ramaswamy Govindan, MD Director Professor of Medicine Director, Thoracic Oncology Program Department
More informationLooking Beyond the Standard-of- Care : The Clinical Trial Option
1 Looking Beyond the Standard-of- Care : The Clinical Trial Option Terry Mamounas, M.D., M.P.H., F.A.C.S. Medical Director, Comprehensive Breast Program UF Health Cancer Center at Orlando Health Professor
More informationManagement of advanced non small cell lung cancer
Management of advanced non small cell lung cancer Jean-Paul Sculier Intensive Care & Thoracic Oncology Institut Jules Bordet Université Libre de Bruxelles (ULB) www.pneumocancero.com Declaration No conflict
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 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 informationMaintenance Therapy for Advanced NSCLC: Which Patients, Which Approach?
Maintenance Therapy for Advanced NSCLC: Which Patients, Which Approach? Mark A. Socinski, MD Visiting Professor of Medicine and Thoracic Surgery Director, Lung Cancer Section, Division of Hematology/Oncology
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 informationMaking the first decision: EGFR mutation-positive NSCLC in the advanced setting
ELCC May 217, Switzerland Making the first decision: EGFR mutation-positive NSCLC in the advanced setting Noemí Reguart, MD, PhD Hospital Clínic de Barcelona, Spain Disclosures Consultant or Advisory Role
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 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 informationPERIOPERATIVE TREATMENT OF NON SMALL CELL LUNG CANCER. Virginie Westeel Chest Disease Department University Hospital Besançon, France
PERIOPERATIVE TREATMENT OF NON SMALL CELL LUNG CANCER Virginie Westeel Chest Disease Department University Hospital Besançon, France LEARNING OBJECTIVES 1. To understand the potential of perioperative
More informationChoosing Optimal Therapy for Advanced Non-Squamous (NS) Non-Small Cell Lung Cancer
Choosing Optimal Therapy for Advanced Non-Squamous (NS) Non-Small Cell Lung Cancer Jyoti D. Patel, MD Associate Professor Feinberg School of Medicine Robert H Lurie Comprehensive Cancer Center Northwestern
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 informationMolecular Analysis for Targeted Therapy for Non- Small-Cell Lung Cancer Section 2.0 Medicine Subsection 2.04 Pathology/Laboratory
2.04.45 Molecular Analysis for Targeted Therapy for Non- Small-Cell Lung Cancer Section 2.0 Medicine Subsection 2.04 Pathology/Laboratory Effective Date November 26, 2014 Original Policy Date November
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 informationImmune Checkpoint Inhibitors for Lung Cancer William N. William Jr.
Immune Checkpoint Inhibitors for Lung Cancer William N. William Jr. Diretor de Onco-Hematologia Hospital BP, A Beneficência Portuguesa Non-Small Cell Lung Cancer PD-1/PD-L1 Inhibitors in second-line therapy
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 informationTargeting Acquired Resistance to EGFR Kinase Inhibitors: Beyond T790M Mutation
Targeting Acquired Resistance to EGFR Kinase Inhibitors: Beyond T790M Mutation James Chih-Hsin Yang, MD, PhD National Taiwan University Hospital National Taiwan University Cancer Center Taipei, Taiwan
More informationMaintenance paradigm in non-squamous NSCLC
Maintenance paradigm in non-squamous NSCLC L. Paz-Ares Hospital Universitario Virgen del Rocío Sevilla Agenda Theoretical basis The data The comparisons Agenda Theoretical basis The data The comparisons
More informationState of the Art Treatment of Lung Cancer Ravi Salgia, MD, PhD
State of the Art Treatment of Lung Cancer Ravi Salgia, MD, PhD Professor and Chair Arthur & Rosalie Kaplan Chair Medical Oncology and Therapeutics Research Nothing to disclose DISCLOSURE Objectives Lung
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 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 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 informationREVIEWS. Personalized medicine in lung cancer: what we need to know. Tony S. K. Mok
Personalized medicine in lung cancer: what we need to know Tony S. K. Mok Abstract Lung cancer is a complex and often fatal disease. The recent discovery of activating mutations in EGFR and fusion genes
More informationIRESSA (Gefitinib) The Journey. Anne De Bock Portfolio Leader, Oncology/Infection European Regulatory Affairs AstraZeneca
IRESSA (Gefitinib) The Journey Anne De Bock Portfolio Leader, Oncology/Infection European Regulatory Affairs AstraZeneca Overview The Drug The Biomarker and Clinical Trials Sampling Lessons Learned The
More informationThe Evolving Role of Adjuvant Therapies
Therapy-predictive markers for adjuvant chemotherapy The Evolving Role of Adjuvant Therapies Micrometastasis Prognostic Markers (BRCA1) Cured No Further Tx Chemosensitive Rafael Rosell th European Perspectives
More informationStrategies in the therapy of advanced NSCLC SAMO Winter-Conference 2008 on Chest tumors
Strategies in the therapy of advanced NSCLC SAMO Winter-Conference 2008 on Chest tumors Miklos Pless Medical Oncology Kantonsspital Winterthur 2 Setting the stage. 1995: Chemotherapy works! Meta-Analysis
More informationThoracic and head/neck oncology new developments
Thoracic and head/neck oncology new developments Goh Boon Cher Department of Hematology-Oncology National University Cancer Institute of Singapore Research Clinical Care Education Scope Lung cancer Screening
More informationMaintenance Treatment of Advanced NSCLC
Maintenance Treatment of Advanced NSCLC Giorgio V. Scagliotti University of Torino Department of Clinical & Biological Sciences giorgio.scagliotti@unito.it UNIVERSTY OF TORINO DEPT. OF OF Maintenance /Consolidation/Sequencing
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 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 informationMonthly Oncology Tumor Boards: A Multidisciplinary Approach to Individualized Patient Care Lung Cancer: Advanced Disease March 8, 2016
Monthly Oncology Tumor Boards: A Multidisciplinary Approach to Individualized Patient Care Lung Cancer: Advanced Disease March 8, 2016 Jae Kim, MD City of Hope Comprehensive Cancer Center Karen Reckamp,
More informationNon-small Cell Lung Cancer: Multidisciplinary Role: Role of Medical Oncologist
Non-small Cell Lung Cancer: Multidisciplinary Role: Role of Medical Oncologist Vichien Srimuninnimit, MD. Medical Oncology Division Faculty of Medicine, Siriraj Hospital Outline Resectable NSCLC stage
More informationMedical Policy An independent licensee of the Blue Cross Blue Shield Association
Proteomic Testing for Systemic Therapy in Non-Small-Cell Lung Cancer Page 1 of 43 Medical Policy An independent licensee of the Blue Cross Blue Shield Association Title: Proteomic Testing for Systemic
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 informationBalazs Halmos, M.D. Division of Hematology/Oncology Columbia University Medical Center
Balazs Halmos, M.D. Division of Hematology/Oncology Columbia University Medical Center Eli-Lilly Pfizer Astellas Daiichi-Sankyo Oncothyreon Astex Astra-Zeneca Bristol-Myers-Squibb Novartis Roche Boehringer-Ingelheim
More informationMutation and prognostic analyses of PIK3CA in patients with completely resected lung adenocarcinoma
Cancer Medicine ORIGINAL RESEARCH Open Access Mutation and prognostic analyses of PIK3CA in patients with completely resected lung adenocarcinoma Zhengbo Song 1,2, Xinmin Yu 1 & Yiping Zhang 1,2 1 Department
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 information