Heidi Roschitzki-Voser1, Rudolf Maibach1, Rolf A. Stahel2 and Solange Peters3
1 ETOP Coordinating Office, Bern
2 Clinic of Oncology, University Hospital Zürich
3 Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne
Keywords: Lung cancer, targeted therapy, EGFR mutation, immunotherapy
meanwhile comprises over 200 participating institutions from all over Europe and beyond (Figure 1).
These members are either single academic hospitals and clinics or collaborative groups like ALTG, Cancer Trials Ireland, CECOG, EORTC, HORG, IFCT, Lung Cancer Group Cologne, SAKK, and SLCG. These groups act as sponsor representatives in their countries, take over some of the responsibilities in the projects and often act as in-termediary between ETOP and their own sites. This pro-vides the necessary flexibility to take into account local requirements and traditions and allows for conducting research in a way, which is familiar for the respective in-vestigators and their staff.
Figure 1: The ETOP Scientific Network
Participation in clinical trials
Participation in translational research projects Participation in both
Collaborative group
SCHWERPUNKTTHEMA: LUNGENKREBS
The first major project initiated by ETOP is Lungscape [8]
a translational research project to study the molecular epi-demiology of lung cancer in Europe, allowing patholo-gists to work hand-in-hands with clinicians. The heart of Lungscape is a decentralized biobank (“iBiobank”) with almost 3000 fully annotated tissue samples from resected stage I-III NSCLC.
From the start, ETOP has also advanced academic clini-cal research by sponsoring therapeutic trials devised and executed in collaboration with its members. ETOP is cur-rently leading seven ongoing clinical trials as sponsor and participates, together with other collaborative groups, in two commercial trials.
The first clinical trial set up by ETOP is BELIEF, which was developed in collaboration with the SLCG. It is a single-arm, multicentre phase II trial that was designed to provide evidence for the combined activity of erlotinib and bevacizumab as first-line therapy for patients with NSCLC and activating epidermal growth factor receptor (EGFR) mutations, stratified by the presence of the pre-treatment T790M allele (i.e., T790M positive or nega-tive) [9].
The results from the BELIEF trial provide further evi-dence that the combination of EGFR and VEGFR inhi-bition may be a promising strategy for further improv-ing the outcomes in patients with NSCLC harbourimprov-ing an activating EGFR mutation. The benefit has proven to be most pronounced for patients carrying also the T790M mutation [9].
The promising results from the BELIEF trial have per-suaded the ETOP investigators to assess the efficacy and tolerability of such a treatment combination in the BOOSTER trial with the third-generation EGFR TKI osimertinib combined with bevacizumab as second-line treatment in advanced NSCLC with activating EGFR and T790M resistance mutation. The BOOSTER protocol was released in December 2016 and is currently under acti-vation in Switzerland, Ireland, the Netherlands, Spain, South Korea, and Singapore.
The encouraging results from immunotherapy trials tar-geting the immune checkpoint pathways in order to trig-ger anti-tumour activity [5, 10] has prompted the ETOP scientific community to expand the research focus into this new field. The STIMULI trial is the first academic ETOP trial with the immune checkpoint inhibitor ipi-limumab in early stage small cell lung cancer. The trial was developed in collaboration with the IFCT and was later amended to an ipilimumab/nivolumab combination treatment in this curative-intent context. Several other ETOP trials involving immune checkpoint inhibitors fol-lowed soon after. The NICOLAS trial is the very first one to analyse the tolerability of nivolumab when given con-currently with definitive radical chemo- and radiotherapy.
PROMISE-meso, an open-label, randomised, phase III
trial comparing pembrolizumab versus standard chemo-therapy for advanced pre-treated malignant pleural meso-thelioma, is the first ETOP trial in this aggressive thoracic malignancy.
Apart from sponsoring its own clinical trials, ETOP also participates in trials from other academic groups where it acts as sponsor representative, taking over some of the responsibilities in the projects. And last but not least, ETOP with its network also participates in commercial clinical trials that are sponsored by the pharmaceutical in-dustry. These kind of collaborations provide access to large and complex international trials that could not be carried out by an academic research organisation alone.
From the first days, it was one of ETOP’s mission to pro-mote the exchange of knowledge and spreading the lat-est insights on thoracic malignancies. The ETOP Confe- rence Slide Decks for example are designed to highlight and summarise key findings in thoracic oncology from the major congresses such as ASCO, ESMO, and the WCLC.
These slide sets are realised with the kind support of Eli Lilly and can be downloaded from the ETOP web-site (www.etop-eu.org). Since the first edition in 2011, the download figures have constantly increased, underlining the value of the Slide Decks to Oncology Healthcare Phy-sicians especially in the rapidly changing and developing landscape of thoracic malignancies.
Another important mainstay are the ETOP Residential Workshops, which have become a successful tradition.
The format of bringing together young investigators and experienced international experts offers a unique opportu-nity to young researchers to exchange research ideas and learn from the experts in the field of thoracic oncology.
The next ETOP Residential Workshop takes place 5-7 October 2017 in Amsterdam, the Netherlands.
In the past few years, pathways have been proposed to im-prove the efficiency of clinical research in Europe, involv-ing the public hospital sector. A central prerequisite in this undertaking is the connection of a disease-oriented network and an integrated infrastructure. The contribu-tion of ETOP in this context is to bring together opin-ion leaders who are ready to feed their share of ideas and research questions into a joint structure that makes it all happen. ETOP adopts a pragmatic and flexible approach, which focuses on how to effectively bring forward projects that are truly promising. The guiding motivation is to maintain the academic control of the research, recognising at the same time that the collaboration with the pharma-ceutical industry is needed and fruitful, and in the best interest of our patients.
Bibliography
1. Chan BA, Hughes BG. Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. Transl Lung Cancer Res 4: 36-54, 2015.
SCHWERPUNKTTHEMA: LUNGENKREBS
Correspondance:
Solange Peters, MD PhD ETOP Scientific Coordinator Department of Oncology
Centre Hospitalier Universitaire Vaudois (CHUV) CH-1011 Lausanne, Switzerland
solange.peters@chuv.ch www.etop-eu.org
2. Reck M, Heigener DF, Mok T, et al. Management of non-small-cell lung cancer: recent developments. Lancet 382: 709-719, 2013.
3. Zappa C, Mousa SA. Non-small cell lung cancer: current treat-ment and future advances. Transl Lung Cancer Res 5: 288-300, 2016.
4. Prendergast GC. Immune escape as a fundamental trait of cancer:
focus on IDO. Oncogene 27: 3889-3900, 2008.
5. Antonia SJ, Larkin J, Ascierto PA. Immuno-oncology combina-tions: a review of clinical experience and future prospects. Clin Cancer Res 20: 6258-68, 2014.
6. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127: 2893-2917, 2010.
7. Stahel R, Baas P, Faivre-Finn C, et al. Meeting report: 2nd meet-ing of the European Thoracic Oncology Platform (ETOP). Lung Cancer 68: 121-124, 2010.
8. Peters S, Weder W, Dafni U, et al. Lungscape: resected non-small-cell lung cancer outcome by clinical and pathological parameters.
J Thorac Oncol 9: 1675-1684, 2014.
9. Rosell R, Dafni U, Felip E, et al. Erlotinib and bevacizumab in patients with advanced non-small-cell lung cancer and activating EGFR mutations (BELIEF): an international, multicentre, single-arm, phase 2 trial. Lancet Respiratory Medicine 2016; in press.
10. Pardoll DM. The blockade of immune checkpoints in cancer im-munotherapy. Nat Rev Cancer 12: 252-264, 2012.
Lago di Luzzone, Blenio.
SCHWERPUNKTTHEMA: LUNGENKREBS
Die Thorax-Onkologie macht Fortschritte. Nebst besser verträglichen Chemotherapien stehen heu-te Immuntherapien und molekulare Therapien zur Verfügung [1]. Die Geschwindigkeit mit der sich das Gebiet entwickelt, stellt die klinische Forschung vor Herausforderungen. Auch die SAKK Projektgrup-pe Lungenkrebs (PGL) ist mit solchen konfrontiert.
Gleichzeitig bieten sich Möglichkeiten und Chancen.
Manche Therapieentscheide in der Onkologie werden nicht evidenzbasiert gefällt, sondern verschiedene Kli-niken verfolgen verschiedene Behandlungskonzepte. In der Thorax-Onkologie betrifft dies vor allem die lokal fortgeschrittenen nicht-kleinzelligen Bronchuskarzinome (NSCLC) und Mesotheliome. Die PGL engagiert sich seit Jahrzehnten für bessere Evidenz bei multimodaler Thera-pie (Chirurgie, RadiotheraThera-pie und ChemotheraThera-pie). Dank der Studie SAKK16/00 wissen wir heute, dass Patienten mit NSCLC im Stadium IIIA (N2) zwar von einer Opera-tion und Chemotherapie profitieren, jedoch nicht von einer präoperativen Radiotherapie [2]. Die Frage ist, wie dieses Wissen im Alltag umgesetzt wird. Die neue bundesgesetz-liche Grundlage für eine schweizweite Krebsregistrierung ermöglicht es, den Einfluss der klinischen Forschung auf die medizinische Versorgung im Land zu beurteilen. Dieses Instrument sollte so bald wie möglich genutzt werden.
Die PGL beteiligt sich an der randomisierten Studie Lun-gART der IFCT (Intergroupe Francophone de Cancérolo-gie Thoracique), um den Nutzen der adjuvante Radiothe-rapie bei NSCLC IIIA und R0-Resektion zu untersuchen.
Leider schreitet die Rekrutierung nur langsam voran. Ein Grund könnte sein, dass die adjuvante Radiotherapie an vielen Zentren als Standard gilt, obwohl Metaanalysen 1998 und 2016 keinen eindeutigen Nutzen zeigten [3].
Die Herausforderung für den Arzt besteht darin, gewisse traditionelle Verfahren zu hinterfragen und dem Anreiz der maximalen Therapie zu widerstehen. Vergleichende Studien, die Therapiestandards definieren, sind prioritär.
Mit mehr Unterstützung durch Behörden und Versiche-rungen würden sie sich schneller realisieren lassen.