Ongoing Lung Cancer Research
in Europe
Rosario García Campelo, MD
Some fun facts about Europe
• Geologically it can be said that Europe is not a continent
• Within Europe 23 official languages and 60 unofficial are
recognized
• At present 51 independent European states are recognized..
But this scenario changes quickly…
• It has the smallest and the largest country in the world
• It has the oldest country of the world
• Italians don't drink cappuccino after 11 AM
• The Sagrada Familia church in Barcelona is taking longer to
build than the pyramids (it was started in 1882 and no, it is not
done yet)
• Disney is the most visited place in Europe
• Europe has the village with the longest name in the world…
Given this heterogeneity…
What about lung cancer
in Europe?
Lung Cancer in Europe
409.000 new cases per year
353.000 deaths per year
Ferlay et al. EJC 2013
In 2015 for the first time, lung cancer mortality rate in Europe will
be superior to breast cancer mortality rate
Malvezzi M et al. Ann Oncol 2015
Therapeutic oncology drug spend per capita 2010-2014
Global New Molecular Entities 2009-2013
(Availability as of 2014)
Let´s talk about research…
Are we playing The Champions League?
Yes we are…
International Distribution of Lung Cancer Clinical Trials
Source: clinicaltrials.gov/
1545 Lung Cancer Trials in Europe
Source: clinicaltrials.gov/
Phase I Trials in Europe
• A growing and dynamic area of activity in Europe
• Clear leadership: France, UK, Germany
Presented by JC Soria, ESMO 2014
European Drug Development Network (EDDN)
• The European Drug Development Network
was created in 2008 in order to address
challenging clinical questions in early cancer
drug development
• 14 leading cancer institutions from
7 European countries
Oncology Platforms in Europe
Platforms for mutation testing
• Regional/ National and International Initiatives
Platform mutation testing in lung cancer
National and regional
• Nationwide provision of molecular tests in France
• National collaboration of academic centers in Netherlands
• UK wide sequencing study of NSCLC
• Network of Genomics Medicine (Cologne, regional)
International
• Lungscape (ETOP)
• SPECTAlung (ETOP and EORTC)
French National INCA Platform
Operated by INCa/Ministry of Health Since 2006
Objective:
• Perform molecular
testing for all patients
• Perform high quality
tests
28 regional centres
• Partnerships between several
laboratories located in University
hospitals and cancer centres
• Cooperation between
pathologists and biologists
Rapid access to innovation
Offer each patient in France an equal access to molecular tests as soon as
a therapy is available
Mid 2008 : EMA approvals for panitumumab and
cetuximab for patients with wild type KRAS
tumours
June 2009 : gefitinib approvals by EMA for patients
with activating mutations of EGFR in their
tumours
 INCa started to allocate €2.5M to the 28 centres at
the end of 2008
=> INCa started to allocate €1.7M to the 28 centres
at the end of 2009
Ensure the best quality for molecular tests
Implementation of a quality assurance programme
• Elaboration of guidelines for:
- the detection of mutations in solid tumors
-
the organization of molecular testing
reports of molecular tests
• Implementation of a national External Quality Assessment for the
28 centres :
– 2011 : BCR-ABL quantification, KRAS and EGFR mutation screening
– 2012: BRAF mutation screening
 Assurance quality optimization
 Guide the molecular genetics centres to becoming accredited to
ISO 15189 standard as soon as possible
Anticipate the launch of new targeted therapies
INCa set up a program for prospective detection of emerging biomarkers :
 EGFR , KRAS, HER2, PI3KCA and BRAF mutations screening and ALK translocation
screening for patients with NSCLC
 KRAS and BRAF mutations screening for patients with colorectal cancer
 BRAF and KIT mutations screening for patients with melanoma
=> Be ready to perform the test as soon as the therapy is available
Spanish Biomarker Platform (SEOM/SEAP)
Center for Personalized Cancer Treatment (CPCT)
Started in 2010
UMCU, EUR, NKI
2014: all academic centers
2014-2015: teaching hospitals
“It is our mission to offer every patient
personalized cancer treatment, which is
based on the genetic features of the patient's
tumor. In this way inefficient treatments can
be prevented and the treatment of cancer can
be optimized.”
The three main activities of the CPCT are:
-To identify common genetic changes in the
DNA of the individual tumor that serve as a
guideline for the treatment of cancer.
-Research on new genetic abnormalities that
can predict the efficiency of a treatment.
-To conduct clinical scientific research, testing
new medicines among a select group of
patients.
www.cpct.nl
Network Genomic Medicine Lung Cancer
Lung Cancer Group Cologne, LCGC
• Founded in 2005 at the Center for Integrated Oncology at the Univ Hospital of Cologne
• The main goal is to develop more effective, personalized treatments for lung cancer
Lung Cancer Group Cologne, LCGC
TRAcking Cancer Evolution Through Therapy (Rx)
842 patients with stage I-IIIA non-small cell lung cancer (NSCLC)
over a three to four year period. Each patient will be followed for
a total of five years.
Main Objective:
Define the relationship between intratumour heterogeneity and
clinical outcome following surgery and adjuvant therapy
Establish the impact of adjuvant platinum-containing regimens
upon intratumour heterogeneity in relapsed disease compared to
primary resected tumour.
Techniques and Technologies
• NGS
• Minimally invasive circulating biomarkers (CTCs, cfDNA)
• Immunology-based techniques
ETOP
• Founded in 2009
• Comprises more than 50 members
• Collaborative groups
• Institutions from all over Europe and beyond
Molecular epidemiology projects
Lungscape
• Lungscape is a decentralised biobank with fully annotated tissue samples from resected stage I III NSCLC
Mesoscape
• Mesoscape is a project to study the molecular epidemiology of malignant mesothelioma in
Europe and has a similar set-up as Lungscape. A number of major cancer centres will contribute
at least 1100 cases diagnosed in the last years
Radioscape
• The Radioscape program aims to address challenges of studying the molecular characteristics of
lung cancer in relation to radiation therapy by coordinating and harmonizing the procedures of a
group of lung cancer specialists working in translational research across Europe, and facilitating
analysis of larger series of cases
The European Thoracic Oncology Platform Lungscape Project:
Clinical outcome data as a basis for molecular correlations in
resected non-small cell lung cancer.
OS by Stage
100
Log rank test: p value <0.001
80
60
40
20
0
Ia
Ib
IIa
IIb
IIIa
IIIb
n=560
n=644
69.6%
63.6%
n=415
n=292
51.6%
47.7%
n=499
29.0%
n=39
13.0%
0 12 24 36 48 60 72 84 96 108 120132144156
Months
Peters S, et al. J Thorac Oncol 2014
Lungscape Master Protocol
Participating Sites
Decentralised Biobanks
Centralised Database
(virtual Biobank)
External Quality Assessments
(if applicable)
Lungscape 001 ALK
Lungscape 002 MET/PI3K/PTEN
Lungscape 003 Multiplex Mutation Testing
Lungscape 004 RANK(L)
Lungscape 005 PD-L1
Overarching Goal
•
•
•
•
Establish decentralised NSCLC bank
Generate biological hypotheses
Establish clinical trial platform
Develop practical diagnostic algorithms
Clinical Trials
STIMULI A randomised open-label phase II trial of consolidation ipilimumab in limited-stage
SCLC after chemo-radiotherapy
SPLENDOUR A randomised, open-label phase III trial evaluating the addition of denosumab
to standard first-line anticancer treatment in advanced NSCLC
NICOLAS A feasibility trial evaluating anti-PD1 nivolumab consolidation after standard firstline chemotherapy and radiotherapy in locally advanced stage IIIA/B NSCLC
NICHE Afatinib in pretreated patients with advanced NSCLC harbouring HER2 exon 20
mutations
Anual Report 2014
ETOP Annual Meeting
ETOP Residential Workshop
European Organization for Research and Treatment of Cancer (EORTC)
• Private and not-for-profit organization created in 1962
• Main mission: promote and conduct research to improve
cancer care
• Core activity: conduct clinical trials
– International
– Multidisciplinary
– Develop new treatments
– Define new standards of care
– Large academic trials
– Integrated & correlative translational research
and biobanking
LUNG CANCER GROUP
14MG Solid tumour panel v1
Panel footprint: 2.2 Mb
Panel features: 478
10
29
111
328
Signalling
Transcription factor
Transcriptional control
Apoptosis
Genes (all exons)
Copy number variants
DNA damage response
Cell cycle control
Miscellaneous/Unknown
Immune-related
Structural components
Function
(genes)
SPECTAlung Master Protocol
EORTC
Clinical Trials Database
Lung
Open study
Study to be open
Closed study
08111
A randomised, open-label phase III trial evaluating the addition of denosumab to standard first-line anticancer
treatment in advanced NSCLC
22113
LungTech Stereotactic Body Radiotherapy (SBRT) of inoperable centrally located NSCLC: A phase II study in
preparation for a randomized phase III trial
08114
Genetics of EGFR Mutation Study (GEM): a Translational Study of the EORTC Lung group
22055
Phase III study comparing post-operative conformal radiotherapy to no post-operative radiotherapy in patients
with completely resected non-small cell lung cancer and mediastinal N2 involvement – LUNG-ART
1335
SPECTAlung: Screening Patients with thoracic tumors for Efficient Clinical Trial Access
1217
Evaluation of 3’-deoxy-3’-[18F]fluorothymidine-PET and diffusion weighted imaging MRI in patients with early
stage non-small cell lung cancer treated with a platinum-based doublet as preoperative chemotherapy
Lung Cancer Group Meeting: Paris – October 2015
Cancer Cooperative Groups, Health Organisations,
and Associations
Lung Cancer Group (EORTC)
European Thoracic Oncology Platform (ETOP)
Arbeitsgemeinschaft Onkologische Thoraxchirurgie (AOT)
Arbeitsgruppe Thorakale Onkologie der Arbeitsgemeinschaft Internistische Onkologie der
Deutschen Krebsgesellschaft (Thorakale-Onkologiegruppe der AIO der DKG)
Associazione Italiana Oncologia Toracica (AIOT)
British Thoracic Oncology Group (BTOG)
Danish Lung Cancer Group (DLCG)
Danish Oncological Lung Cancer Group (DOLG)
European Lung Cancer Working Party (ELCWP)
Groupe français de Pneumo-Cancerologie
Grupo Español de Cáncer de Pulmón
Groupe Francais de Pneumo-Cancerologie (GFPC)
Intergroupe Francophone de Cancerologie Thoracique (IFCT)
Leuven Lung Cancer Group (LLCG)
Lung Cancer Group Cologne
Manchester Lung Cancer Group
Medical University of Gdansk “TOP” Group
National Cancer Research Institute - Lung Cancer Clinical Study Group (NCRI)
Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose (NVALT)
Norwegian Lung Cancer Group (NLCG)
Project Group Lung Cancer of the Swiss Group for Clinical Cancer Research (SAKK)
Swedish Lung Cancer Study Group
Thoracale Oncologie Groep Antwerpen (TOGA)
Dutch Society of Physicians for Pulmonology and
Tuberculosis - NVALT
N
V
A
L
T
NVALT 8: A randomized phase II study of adjuvant chemotherapy with or without lowmolecular weight heparin in completely resected NSCLC patients.
NVALT-11: A randomized phase III study of prophylactic Cranial Irradiation (PCI) versus
observation in radically treated patients with stage III NSCLC.
NVALT-12: A randomized phase II study of Paclitaxel-Carboplatin-Bevacizumab with or
without nitroglycerin patches in patients with stage IV non-squamous NSCLC.
NVALT-15: Phase II study with oral fibroblast growth factor-1 inhibitor BIBF1120 as second
line treatment in lung carcinoma patients harbouring fibroblast growth factor receptor-1 gene
amplification. Collaboration with Spanish Lung Cancer Group.
NVALT-16: Iressa RE-challenge in advanced NSCLC EGFR mutated patients who
responded to an EGFR-TKI used as first or previous treatment.
NVALT-17: A randomized phase III study of erlotinib compared to intercalated erlotinib with
cisplatinum pemetrexed as first-line therapy for advanced EGFR mutated NSCLC.
NVALT-18: A randomized phase II study comparing second line monotherapy erlotinib,
docetaxel and intercalated erlotinib docetaxel in relapsed EGFR wild type, ALK negative
non squamous cell carcinoma patients.
NVALT-19: Switch maintenance treatment with gemcitabine for patients with malignant
mesothelioma who do not progress after 1st line therapy with a pemetrexed-platinum
combination. A randomised open label phase II study.
NVALT-22: First line chemotherapy in KRAS mutated non-small cell lung cancer patients: a
phase III comparing cisplatin-pemetrexed with carboplatin-paclitaxel-bevacizumab.
NVALT-24: A phase III prospective double blind placebo controlled randomized study of
adjuvant medi4736 in completely resected non-small cell lung cancer. Collaboration with
Australian Group.
NVALT-25: ELDAPT: Elderly with locally advanced Lung cancer: Deciding through geriatric
Assessment on the oPtimal Treatment strategy.
IFCT: Intergroupe Francophone
de Cancerologie Thoracique
• Created in 1999, IFCT is a multidisciplinary group of experts sponsoring clinical
research to improve the survival and quality of life of patients with lung cancer
• The main goals of the association are:
– To facilitate the development of clinical and translational research in thoracic oncology
– To provide lifelong learning for oncology professionals and share information on thoracic
oncology
– To foster epidemiologic research and prevention studies
– To promote the evaluation of clinical practice in thoracic oncology
– IFCT projects are coordinated by a Clinical Research Unit accredited by the National Cancer
Institute (INCa) and the National League Against Cancer
IFCT in Figures…
• Nearly 9,000 patients included in 28 studies
• 300 centers across France
• 600 investigators
• 19 people - Clinical Research Unit staff
Ongoing Trials
Indication
Schemas
Centers
Inclusions
Objective
IFCT-0503 Lung ART
IIIA-N2
Mediastinal pN2 conformational
radiotherapy
36
295
700
IFCT-1001 CHIVA
HIV+
Pemetrexed + Carboplatin
40
55
62
IFCT-1003 LADIE
Women
Fulvestrant with or without
EGFR-TKI
63
233
394
IFCT-GFPC-1101
Maintenance
Stage IV
Adapted maintenance to
inclusion treatment response
94
712
938
IFCT-1201 MODEL
Elderly Patients
Maintenance chemotherapy
82
333
546
IFCT 4-12 STIMULI
Limited SCLC
Immunotherapy
after chemotherapy
18
11
325
IFCT-1301
SAFIR 02 Lung
Stage IV
Efficient and highly rated
technologies to guide therapeutic
decision-making
22
127
650
IFCT-1302 CLINALK
ALK+
Therapeutic care after
progression on crizotinib
84
318
300
BTOG: British Thoracic Oncology Group
• Founded in 2002, chair Ken O´Byrne
• BTOG Chair: Sanjay Popat
• BTOG are a not for profit organisation within
the NHS
• Multidisciplinary Group:
• BTOG represents all the disciplines
involved in the care of lung cancer and
mesothelioma throughout the UK and
includes over 2000 medical and clinical
oncologists, respiratory physicians,
surgeons, radiotherapists, radiologists,
nurses, pharmacists and scientists.
• BTOG is kindly hosted by UHL NHS Trust
and is based at Glenfield Hospital, Leicester
SLCG: Spanish Lung Cancer Group
• Multicenter cooperative group for treatment and research in
lung cancer
• Founded in 1991 by Dr. Rosell
• Chair: Dr. Mariano Provencio
• Members:
–
–
–
–
Medical oncologists
Thoracic Surgeons
Basic researchers
Radiotherapists
SLCG
STRUCTURE
 6CRA
 2 administrative support
SERVICES
Administration Unit
 Maintaining group files
 Activity reports
 Institutional and internal Communication
 Events organization
Clinical Operation Unit
 Regulatory Affairs
 Project management
 Monitoring
 Data management
 Pharmacovigilance
 Statistics
SLCG
• 2014 affiliates:
–
–
–
–
–
346 members
144 centers
32 centers with thoracic surgery facilities
Cancer Biology Labs Network
Central lab: Institut Català d´Oncologia, Hospital Germans Trias i Pujol, Badalona
• Working groups:
– Thoracic surgeons
– Mesothelioma
• Multinational cooperative studies
–
–
–
–
–
Promoted by GECP
Agreement with pharma industry
GECP Central Labs / Biobanks
Other countries
Laboratories in other countries
SLCG: Total number of treated patients in own studies
Small Cell Lung Cancer
932
NSCLC (Initial Stages)
1462
Advanced NSCLC
6733
Other Projects
4723
TOTAL
13,849
SLCG: Published Papers
Revista
Magazine
The
England
Journal Journal
of Medicineof
TheNew
New
England
Número
Number
of articles
Medicine
22
PLoS One
PLoS One
22
Journal Clinical Oncology
Journal of Clinical Oncology
99
Annals of Oncology
55
Annals of Oncology
Lung Cancer
Lung Cancer
9
12
Clinical Cancer Research
Clinical Cancer Research
85
Clinical Lung Cancer
Clinical Lung Cancer
66
Seminars in Oncology
Seminars in Oncology
55
Lancet Oncology
2
Lancet Oncology
1
SLCG ongoing clinical trials
GOAL: Phase I-II randomized study to evaluate treatment with Gefitinib with or without Olaparib according
to EGFR mutations (Exon 19 Deletion or L858R with or without T790M) and BRCA1 mRNA expression in
patients with Advanced NSCLC
Serial rebiopsy project in EGFR mutant NSCLC
Dabrafenib plus trametinib in BRAF-mutant advanced NSCLC
EUCROSS. Phase II trial to evaluate efficacy and security of crizotinib in ROS1 advanced NSCLC
STIMULI . Phase II randomized trial of consolidation ipilimumab after chemoradiotherapy in limited stage
small cell lung cancer
SPLENDOUR. Phase III trial comparing denosumab plus chemotherapy vs conventional chemotherapy
BEMME Mesothelioma database
INTERNATIONAL COLLABORATION
SLCG and GFPC
EUCROSS TRIAL (SLCG and CIO)
Phase II trial to evaluate efficacy and security of crizotinib
in ROS+ advanced NSCLC
Promoter: University of Cologne
Co investigators: Dr. J Wolf, Dr. Rosell
CIO-SLCG
Spain:
12 open centers
236 from 29 centers
LINC-BR31
A Phase III prospective double blind placebo controlled
randomized study of adjuvant MEDI4736 in completely resected
NSCLC
Promoter: NCIC
A Lung Inmunotherapy NSCLC Consortium (LINC) Trial of the NCIC
CTG, IFCT, CEEOG, NCI-Naples, NVALT, KCSG, ALTG and NHMRC
CTC, SLCG
NVALT 15 (SCLG and NVALT)
Phase II study with oral fibroblast growth factor-1 inhibitor BIBF1120 as second line
treatment in lung carcinoma patients harbouring fibroblast growth factor receptor-1 gene
amplification. Collaboration with Spanish Lung Cancer Group
BELIEF TRIAL
• Open label, phase II clinical trial of erlotinib and bevacizumab in advanced non-small
cell lung cancer patients with EGFR mutations
PIPSeN: IGR/ SLCG
European Initiative in Quality: ERS TASK FORCE
Objective: investigate current practice in lung cancer across Europe
Quality Management
Aspiration: to improve the estándar of care across Europe
• Identify inequalities
• Data collection
• Minimum and gold standards
• Account for social and healthcare infrastructure
4 projects:
• A narrative literature search on quality management of lung cancer
• A survey of national and local infrastructure for lung cancer care in Europe
 38 European countries, 350 centres
 Surveys on national and local levels
• A benchmarking project on the quality of (inter)national lung cancer guidelines
in Europe
• A feasibility study of prospective data collection in a pan-European setting.
Blum et al Eur Respir J 2014
First Comprehensive Snapshot on Lung Cancer in Europe
Blum et al Eur Respir J 2014
Professionals Providing the Majority of Specific Modalities of Lung Cancer Care by Country
Blum et al Eur Respir J 2014
Histological Confirmation Rate
Rich et al. ELCC 2015
Resection Rates
Rich et al. ELCC 2015
Distance Travelled by Patients and Waiting Times
for Thoracic Surgery
Lung Cancer Patient Care
PHYSICAL
OCCUPATIONAL
SOCIAL
PSYCHOLOGICAL
Women Against Lung Cancer
WALCE Association is a non-profit organization
founded in 2006 as an italian-spanish initiative
WALCE aims to be the first association to
function on a European scale in the fight against
lung cancer.
ICAPEM (Association for the Research of Lung Cancer in Women)
Medical association focused on
• Promoting awareness and knowledge about the impact of lung cancer, particularly in women
• Working for the prevention of lung cancer, especially fighting against smoking
• Finding resources to increase research on the different lung cancers according to sex
• Promoting young researchers in the development of their professional careers in researching lung
cancer
Some notes to conclude…
• Lung Cancer Research in Europe is in good health
• Regional, national and international platforms for molecular testing are being
developed all around Europe, although access to such platforms is still
geographically restricted
• A plethora of clinical trials ongoing…
– Innovative forms for collaboration are needed
– Regulatory complexity may be an issue
• Maximize networking opportunities and inter-professional interaction
• Quality management of lung cancer in Europe: a challenge
• Maybe we are missing some global initiatives, like…
BARACK OBAMA, some months ago…
“I want the country that eliminated polio
and mapped the human genome TO
LEAD A NEW ERA OF MEDICINE — one
that delivers the right treatment at the
right time”
Precision Medicine Initiative would "bring
us closer to curing diseases like cancer "
and "give all of us access to the
PERSONALIZED INFORMATION we need
to keep ourselves and our families
healthier."
There is room for improvement in Europe…