etop European Thoracic Oncology Platform c/o IBCSG Effingerstrasse Bern Phone Fax

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1 Annual Report 2015

2 etop European Thoracic Oncology Platform c/o IBCSG Effingerstrasse Bern Phone Fax UBS AG Postfach CH-8098 Zürich Switzerland Account no: Q IBAN: CH Q SWIFT: UBSWCHZH80A 2 P a g e

3 INDEX EDITORIAL 4 KEY DATA 5 ETOP MILESTONES IN ETOP PROJECTS AND TRIALS 6-10 Translational research projects Clinical trials SCIENTIFIC CONTRIBUTION MEETINGS / ACTIVITIES ETOP COLLABORATION WITH IBCSG 15 GROUP STRUCTURE 16 Organigram Members ETOP ORGANIZATION 17 Foundation Council Scientific Committee Scientific Coordinator Independent Data Monitoring Committee FINANCIAL STATEMENT 18 3 P a g e

4 EDITORIAL February 2016 Dear Reader With the annual report 2015 we would like to inform you about our activities during the past year was once again a very busy and successful year, with many ETOP contributions to several international lung cancer congresses. One of the most important ETOP highlights was the presentation of results from the first ETOP trial. An abstract with the first BELIEF results has been selected as best abstract for presentation in the presidential session at the 18th ECCO 40th ESMO European Cancer Congress in Vienna. In addition, the Lungscape projects continued to bear fruits with presentations at several international meetings. We take this opportunity to thank you for your continued partnership and collaboration and for your valuable contribution to the success of ETOP. With this annual report ETOP would like to provide you with an update on its projects, trials and activities. Enjoy reading! Kind regards Prof. Rolf A. Stahel President, ETOP Foundation Council Prof. Solange Peters Communication Chair and Scientific Coordinator ETOP 4 P a g e

5 KEY DATA Publications 2015 Overall Full publication 0 5 Abstracts 5 19 Meeting contributions 2015 Overall Oral presentations 3 11 Posters 2 11 Clinical trials overall Closed trials 0 Open trials 7 Trials with completed accrual 2 Recruiting trials 5 Newly activated trials in Number of patients included 2015 Overall Clinical trials Observational studies 2845 ETOP MILESTONES IN 2015 New ETOP website At the beginning of the year we made some updates and improvements on the ETOP website ( to make the page more user-friendly. The most important changes include a simplified menu and the replacement of the erooms. The new website was launched in March P a g e

6 ETOP web presence Since 2015, ETOP is present on LinkedIn with an own company page ( and also on Wikipedia, where information about the ETOP Lungscape project can be found ( Solange Peters promoted to professor at the University of Lausanne Solange Peters is communication chair and the scientific coordinator of ETOP as well as the chair of several ETOP trials. She is currently teaching at the University of Lausanne and treating patients at the department of oncology at the University Hospital of Lausanne (CHUV) where she is building a translational programme in collaboration with the molecular oncology laboratory directed by Douglas Hanahan and Etienne Meylan at the Swiss Federal Institute of Technology in Lausanne and the Ludwig Institute. Solange Peters received the title of Lausanne University Private Docent (PD-MER) in In November 2015, Solange Peters was promoted to associate professor at the University of Lausanne. We sincerely congratulate her to this very important career step and wish her continued success. ETOP PROJECTS AND TRIALS Translational research projects Lungscape Lungscape continued to demonstrate what a successful translational research project it is. Lungscape 002 MET was selected for oral presentation at the 16th World Conference on Lung Cancer (WCLC 2015), which took place in Denver, USA in September Erik Thunnissen presented the work on behalf of the Lungscape colleagues, stepping in for Lukas Bubendorf (Basel University Hospital, Lungscape Steering Committee and lead of the MET project). 6 P a g e

7 The Lungscape substudy on ALK RT-PCR was also presented at the WCLC poster session.igor Letovanec (CHUV Lausanne, ALK RT-PCR lead) presented the poster, together withsolange Peters (CHUV Lausanne, Lungscape Steering Committee and ETOP Scientific Coordinator). Keith Kerr (Aberdeen Royal Infirmary, Aberdeen University Medical School, Lungscape Steering Committee, ETOP Foundation Council) delivered the Lungscape 003 Multiplex Mutation Testing results, which had been selected for oral presentation at the 18th ECCO - 40th ESMO European Cancer Congress, Vienna, Austria, on 26 September While these presentations were delivered in autumn, the Lungscape participating sites were immersed in scoring the Lungscape TMA s for the Lungscape 002 PTEN IHC project. Digital image analysis continues at University Hospital of Zurich with Alex Soltermann (PTEN lead) and statistical analysis is ongoing at the ETOP Statistical Center, Frontier Science Foundation Hellas. Abstracts will be submitted to ESMO 2016, and to ESP The Lungscape 005 PD-L1 project started with the DAKO-mandated PD-L1 trainings (staining and scoring). The PD-L1 study results are highly anticipated, and are expected for presentation at the end of Mesoscape Key milestones that are being reached are the establishment of the Mesoscape cohort and biobank. Medical review is ongoing by the study co-chairs Paul Bass (NKI Amsterdam) and Isabelle Schmitt-Opitz (University Hospital Zurich). Biomarker studies will start later in Fixation Effect Study This project was initiated by ETOP in 2015, and is led by Erik Thunnissen (VUMC Amsterdam), to examine the effect of fixation delay / over-fixation on NSCLC and normal components on protein levels (by IHC), DNA (by mutation analysis) and RNA. 28 of the expected 30 cases have already been collected. 7 P a g e

8 Clinical trial ETOP 2-11 BELIEF BELIEF is an open-label, single-arm, phase II multicentre trial exploring whether firstline erlotinib plus bevacizumab improves progression-free survival in NSCLC patients with activating EGFR mutations (del19 or L858R). The outcomes are tested overall and separately in patients with and without the pre-treatment EGFR T790M gatekeeper mutation. The accrual goal of 102 patients was reached in October An abstract with the first results has been submitted to the 18th ECCO 40th ESMO European Cancer Congress in Vienna and was selected as best abstract for oral presentation in one of the presidential sessions. Rolf Stahel, ETOP president and trial co-chair presented the work on behalf of the trial team. ETOP 3-12 EMPHASIS-lung In the EMPHASIS-lung trial, the predictive value of Veristrat, a serum proteomic test, was assessed regarding the efficacy of erlotinib in pre-treated patients with advanced squamous cell lung carcinoma. Over 50 centres from several European countries were activated and by the end of January 2013, 81 patients were randomized. Recruitment was terminated prematurely due to an accrual rate that was deemed insufficient and publication of new data from another study. A pooled analysis with a similar trial conducted in all advanced NSCLC subtypes was presented at ASCO Manuscript preparation, presenting the final results, is ongoing. ETOP / IFCT 4-12 STIMULI STIMULI is a randomised open label phase II trial of consolidation ipilimumab in limitedstage SCLC after chemo-radiotherapy The trial has been activated in France, Switzerland, Spain and the Netherlands, with 40 patients being enrolled and 18 randomized by the end of The recruitment is clearly behind schedule and the trial committee has decided to take action. Several changes were introduced to the protocol, in particular relaxing the inclusion criteria in order to enhance recruitment of patients. Recently communicated results suggest that the combination of ipilimumab with nivolumab may yield substantially higher efficacy. In accordance with BMS, the manufacturer of both drugs, the STIMULI trial protocol was amended to revise the induction phase of the immunotherapy by adding nivolumab to ipilimumab, and to continue in the maintenance phase 8 P a g e

9 with a flat dose of nivolumab alone. The introduced changes present a chance to make the trial substantially more attractive. The amended protocol was released on 21 September 2015 and site activation is ongoing. ETOP 5-12 / EORTC SPLENDOUR SPLENDOUR is a randomised, open-label phase III trial evaluating the addition of denosumab to standard first-line anticancer treatment in advanced NSCLC. Denosumab is a monoclonal antibody targeting and inhibiting RANKL, a protein that acts as the primary signal for bone resorption. The purpose of this study is to investigate the potential of the combination of standard treatment (chemotherapy) with denosumab as compared to the standard treatment alone to increase survival of patients with advanced NSCLC with or without bone metastasis in advanced unselected treatment-naïve patients. ETOP is the sponsor of this trial, which is conducted in collaboration with EORTC as coordinating group patients will be enrolled within approximately 3 years. The first patient was enroled on 12 January 2015 and the overall accrual by 31 December 2015 was 289 patients. ETOP 6-14 NICOLAS Over the past decade, sequential or concomitant chemo-radiotherapy have become the treatment of choice for stage III NSCLC. One attempt to improve the long-term survival is an immunotherapeutic strategy targeting PD-1, a cell surface molecule on activated T-cells that abrogates the anti-cancer immune response. Nivolumab, a monoclonal antibody, is able to prevent the interaction between PD-1 and its ligands. This feasibility trial evaluates nivolumab consolidation treatment in patients with locally advanced stage III NSCLC treated with standard first-line chemotherapy and radiotherapy. The trial protocol was distributed for activation in February 2015 and the first patient was enroled on 25 November 2015 in Spain. ETOP 7-14 NICHE Afatinib in pre-treated patients with advanced NSCLC harbouring HER2 exon 20 mutations. The primary objective of this trial is to evaluate the ability of afatinib, a selective irreversible small molecule inhibitor of the erbb family of proteins, to control disease in pre-treated patients with advanced NSCLC harbouring HER2 exon 20 mutations. The 9 P a g e

10 trial will be conducted at six sites from five different countries, with Spain and Switzerland being already activated. The trial protocol was distributed in December 2014 and the first patient was enroled in September 2015 in Spain. ETOP 8-15 / EORTC 1416 PEARLS PEARLS is a randomized phase III trial with pembrolizumab versus placebo for patients with early stage NSCLC after resection and completion of standard adjuvant therapy. Surgical resection is the standard treatment for operable patients with stage I-IIIA NSCLC. Despite recent advances in staging, post-operative support and adjuvant chemotherapy, a large fraction of patients will still develop recurrence and die of their disease within five years of resection. Hence, there is a need to identify new treatment strategies that can increase the efficacy of adjuvant treatment. Pembrolizumab is a monoclonal antibody, highly specific for binding to the immune checkpoint receptor PD-1 and thus inhibiting the interaction of PD-1 with its ligands PD-L1 and PD-L2. PEARLS is an international, triple-blinded, placebo-controlled randomized phase III trial. It will prospectively investigate adjuvant treatment with pembrolizumab for 1 year versus placebo in early stage NSCLC patients, after completion of radical surgery (lobectomy/pneumonectomy) with or without standard adjuvant chemotherapy. The accrual goal is 1380 randomized patients, 690 in each arm. MSD Merck Sharp and Dohme is the sponsor for this trial in all participating countries. EORTC is coordinating the trial with ETOP as collaborative group. SCIENTIFIC CONTRIBUTIONS IN 2015 Published abstracts Stahel RA, Dafni U, Gautschi O, Felip E, Curioni-Fontecedro A, Peters S, Massutí B, Cardenal F, Aix SP, Früh M, Pless M, Popat S, Kotsakis A, Cuffe S, Bidoli P, Favaretto A, Carcereny E, Sanchez Ronco M, Molina MA, Rosell R. A phase II trial of erlotinib (E) and bevacizumab (B) in patients with advanced non-small-cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations with and without T790M mutation. The Spanish Lung Cancer Group (SLCG) and the European 10 P a g e

11 Thoracic Oncology Platform (ETOP) BELIEF trial. Presented at the European Cancer Congress in Vienna, AT. Eur J Cancer 51 (suppl 3):S711. (ETOP 2-11 BELIEF) Kerr KM, Dafni U, Schulze K, Thunnissen E, Bubendorf L, Hager H, Gately K, Biernat W, Vliegen L, Hernandez Losa J, Marchetti A, Cheney R, Warth A, Speel EJ, Blackhall F, Molina MA, Shames DS, Peters S, Stahel R, On behalf of the ETOP Lungscape investigators. Prevalence and clinical association of gene mutations through Multiplex Mutation Testing in patients with NSCLC: Results from the ETOP Lungscape Project. Presented at the European Cancer Congress in Vienna. Eur J Cancer 51 (suppl 3):S595. (ETOP Lungscape) Bubendorf L, Dafni U, Finn SP, Warth A, Savic S, Thunnissen E, Sejda A, Verbeken EK, Tischler V, Marchetti A, Sansano I, Speel EJM, Cheney R, Nonaka D, Monkhorst K, Di Lorito A, Consuelo Calabuig M, Reidy M, Hager H, Mathieson W, Martorell M, Baas P, Dienemann H, Smit EF, Blackhall FH Dingemans AMC, Felip E, Adjei A, Meldgaard P, Weder W, Vansteenkiste J, Dziadziuszko R, Tsourti Z, Kerr KM, Schulze K, Das-Gupta A, Peters S, Stahel RA. Prevalence and clinical association of MET gene amplification in patients with NSCLC: Results from the ETOP Lungscape Project. Presented at WCLC 2015 in Denver, CO. Journal of Thoracic Oncology, 10(9 suppl 2):S247. (ETOP Lungscape) Letovanec I, Peters S, Tsourti Z, Finn SP, Soltermann A, Bubendorf L, Speel EJM, Marchetti A, Nonaka D, Hager H, Martorell M, Monkhorst K, Sejda A, Cheney R, Sansano I, Verbeken EK, Tischler V, Savic S, Di Lorito A, Consuelo Calabuig M, Felip E, Adjei A, Warth A, Baas P, Meldgaard P, Blackhall FH, Dingemans AMC, Dienemann H, Dziadziuszko R, Vansteenkiste J, Kammler R, Dafni U, Kerr KM, Thunnissen E, Stahel RA. Evaluation of RT-PCR methodology for ALK assessment in patients with NSCLC in Europe: Results from the ETOP Lungscape Project. Presented at WCLC 2015 in Denver, CO. Journal of Thoracic Oncology, 10(9 suppl 2):S693-S94. (ETOP Lungscape) Peters S, Smit EF, Dafni U, Aix SP, Massuti B, Gautschi O, Coate L, López Martín A, van Heemst R, Berghmans T, Meldgaard P, Cobo Dols M, Garde Noguera J, Floriani 11 P a g e

12 IC, Kassapian M, Chittazhathu Kurian Kuruvilla Y, Gasca-Ruchti A, Zielinski C, Gregorc V, Stahel RA and EMPHASIS Collaborative Group. Randomized phase III trial of Erlotinib vs. Docetaxel in patients with advanced squamous cell non-small cell lung cancer (SqNSCLC) failing first line platinum based doublet chemotherapy stratified by VeriStrat Good vs VeriStrat Poor. The European Thoracic Oncology Platform (ETOP) EMPHASIS trial. Presented at ASCO 2015 in Chicago, IL. Journal of Clinical Oncology 33 (suppl 15: 8049) (ETOP 3-12 EMPHASIS) Oral presentations Lung neuroendocrine tumors: Correlation of ubiquitinylation and sumoylation with nucleo-cytosolic partitioning of PTEN. Presented at the 4th International Conference on Translational Medicine (OMICS) in Baltimore Maryland (26-28 October 2015) by Alex Soltermann, on behalf of the Lungscape consortium. A phase II trial of erlotinib (E) and bevacizumab (B) in patients with advanced non-smallcell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations with and without T790M mutation. The Spanish Lung Cancer Group (SLCG) and the European Thoracic Oncology Platform (ETOP) BELIEF trial. Presented at the 18th ECCO-40th ESMO European Cancer Congress (ECC) 2015 in Vienna, Austria (25 29 September 2015) by Rolf A. Stahel, for the BELIEF collaborative group. Prevalence and clinical association of gene mutations through Multiplex Mutation Testing in patients with NSCLC: Results from the ETOP Lungscape Project. Presented at the 18th ECCO-40th ESMO European Cancer Congress (ECC) 2015 in Vienna, Austria (25 29 September 2015) by Keith M. Kerr, on behalf of the Lungscape consortium. Prevalence and clinical association of MET gene amplification in patients with NSCLC: Results from the ETOP Lungscape Project. Presented at the 16th World Conference on Lung Cancer in Denver, Colorado (6 9 September 2015) by Erik Thunnissen, on behalf of the Lungscape consortium. 12 P a g e

13 Poster presentations Igor Letovanec and Solange Peters et al. Evaluation of RT-PCR methodology for ALK assessment in patients with NSCLC in Europe: Results from the ETOP Lungscape Project. Presented at the 16th World Conference on Lung Cancer in Denver, Colorado (6 9 September 2015). Poster # Solange Peters et al. Randomized phase III trial of Erlotinib vs. Docetaxel in patients with advanced squamous cell non-small cell lung cancer (SqNSCLC) failing first line platinum based doublet chemotherapy stratified by VeriStrat Good vs VeriStrat Poor. The European Thoracic Oncology Platform (ETOP) EMPHASIS trial. Presented at the 16th World Conference on Lung Cancer in Denver, Colorado (6 9 September 2015). Poster # MEETINGS / ACTIVITIES IN 2015 Several meetings with a high-level scientific exchange took place also in Furthermore, various ETOP representatives participated to a number of meetings with pharmaceutical industry regarding further ETOP research avenues. Foundation Council Meetings 16 April 2015 ELCC, Geneva 13 November 2015 ETOP Annual Meeting, Zürich Independent Data Monitoring Committee Meetings 8 April 2015 by telephone conference 8 July 2015 by telephone conference 1 October 2015 by telephone conference Meetings under auspices/in collaboration with ETOP BTOG, January 2015, Dublin, Ireland ELCC, April 2015, Geneva, Schweiz 13 P a g e

14 ETOP Annual Meeting The ETOP Annual Meeting was held November 2015 at the University Hospital Zürich, Switzerland. Ongoing projects and trials as well as new ideas and concepts were presented and discussed either during the plenary meeting or in the breakout sessions. More than 100 participants from over 20 countries attended the meeting and used the occasion as an opportunity to engage in stimulating scientific exchange with other ETOP participants. These lively discussions continued also during coffee breaks and the dinner party in honour of Rolf Stahel s birthday. ETOP Residential Workshop The fourth ETOP Residential Workshop was held August 2015 in Amsterdam, Netherlands. Twenty-five young thoracic oncology investigators from twelve countries attended the workshop. The program focused on current trends in research and cancer care. Fifteen lung cancer experts contributed presentations on the therapy of advanced disease, developments in lung cancer radiotherapy, developmental therapeutics, molecular testing, thymoma and conduct of clinical trials. Selected hot topics of this year s workshop were targeted therapies beyond EGFR and ALK as well as immunotherapy. A presentation on lung cancer screening and smoking cessation concluded the program. Furthermore, all participants were asked to bring their own research project, which were presented and discussed in three different groups, each chaired by two or three senior scientists from the faculty. The excellent presentations were followed by lively discussions that were continued over coffee breaks and dinners. The workshop was financed by ESMO through an educational grant and the generous support from Amgen, Boehringer Ingelheim, BMS and Lilly. Educational and collaboration activities One of the missions of ETOP is to serve as meeting platform for European study groups and institutions engaged in research on thoracic malignancies. ETOP promotes the ex- 14 P a g e

15 change of ideas and research in the field of thoracic malignancies. It sponsors and manages an increasing number of translational research projects and clinical trials with an emphasis on advancing the knowledge in thoracic malignancies. Our website ( hosts a series of scientific resources for scientists in the field of lung cancer, such as the conferences slide decks, video news, as well as access to the journal Lung Cancer. ETOP conferences slide decks The ETOP conferences slide decks are designed to highlight and summarise key findings in thoracic oncology from the major congresses like ASCO, ESMO and WCLC. These slide sets are realized with the kind support of Eli Lilly. The slide decks find widespread recognition as indicated by the number of downloads (see table below). ASCO 2015 WCLC 2015 ECC 2015 English Japanese French Italian Total downloads 483* * The download number 2015 was lower than normal for ASCO2015. This was due to restructuring of the ETOP website and the ASCO requirement that registration is needed to download the slides; a feature that had to be developed first. ETOP COLLABORATION WITH IBCSG In order to complete the various tasks entailed by all these projects, ETOP has undergone a strategic collaboration with the International Breast Cancer Study Group IBCSG and its Coordinating Centre in Berne. The ETOP Coordinating Office is hosted by IBCSG and supports all activities in the above projects. In addition, Frontier Science Hellas, a non-profit organisation based in Athens, Greece, is providing statistical expertise for all ETOP projects. 15 P a g e

16 GROUP STRUCTURE The European Thoracic Oncology Platform (ETOP) is a not-for-profit foundation under Swiss law with the purpose of promoting information and research in the field of thoracic malignancies. ETOP Organigram Members ETOP includes 54 leading European groups and institutions, as well as an institution in the USA and in China with a focus on clinical and translational research in thoracic oncology. 16 P a g e

17 ETOP ORGANIZATION Foundation Council President: Rolf. A. Stahel, Switzerland Paul Baas, Netherlands, Keith Kerr, U.K., Kenneth O Byrne, Australia, Rafael Rosell, Spain, Suresh Senan, Netherlands, Walter Weder, Switzerland, Christoph Zielinski, Austria Scientific Committee Chair: Rolf A. Stahel, Switzerland Tetsuya Mitsudomi, Japan, Paris Kosmidis, Greece, Fortunato Ciardiello, Italy Scientific Coordinator Solange Peters, Switzerland Independent Data Monitoring Committee Jean-Pierre Armand, France Oncologist, IDMC chairman Richard Gelber, USA Biostatistician Nick Thatcher, U.K. Oncologist Renato Galeazzi, Switzerland Bioethics Paul Van Houtte, Belgium Radiation Oncologist 17 P a g e

18 FINANCIAL STATEMENT 2015 (IN THOUSAND CHF) All ETOP trials with full academic independence from the pharmaceutical industry, even if sponsored wholly or in part by industry. The financial statements have been audited and approved by KPMG on 1 April, Income Income from collaboration with industry Further research grants Total Expenses Contributions to members, participating centres Pathology, translational research Production slide decks, training Website, internet Scientific exchange and coordination, travel expenses Personnel costs and external services (database, statistics, etc.) Insurance, consulting, financial audit Administrative costs Currency exchange Total P a g e