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A few pearls from ELCC 2017

by Stefan Zimmermann

The 7th edition of the European Lung Cancer Conference (ELCC) took place 5-8 May 2017 in Geneva. From a solid education congress, it seems to have evolved over the years to a high-level forum where critical issues we face as thoracic oncologists are discussed, and cutting-edge new research is presented.  In case you missed it, be sure to catch up some of this year’s highlights through the webcasts.

Introducing the microorganisms colonizing our airways: any role in lung cancer?

In an iconoclastic educational session named “Molecular understanding of lung cancer: the role of the host and the environment”, the role of the microbiome in lung cancer was explored by W. Cookson. With mounting evidence that our commensal and symbiotic microorganisms play a key role in the response to therapy, the interest in modulating our microbiome to optimize and fine-tune lung cancer immunotherapy is immense. For an interesting read, refer to “Microbiota, a key orchestrator of cancer therapy” by S. Roy and G. Trinchieri in Nature Reviews Cancer 2017. Building on the retrospective finding that the gut microbiome of melanoma patients exhibits significant differences between responders and non-responders to PD-1 inhibition, clinical trials aiming at modulation the gut microbiome are now expect to launch imminently, including one at the MD Anderson in collaboration with the Parker Institute for Cancer Immunotherapy.

Think of it as a village: can different clones in a tumour form symbiotic relationships with each other?

In the same session, M. Janiszewska elaborated her fascinating animal model of clonal symbiosis, further expanding our understanding of tumour heterogeneity, where different subclonal cancer cell populations compete and synergize for growth in a symbiotic manner. Tumours represent a complex dynamic ecological system, where seemingly minor clones are nonetheless essential for tumour growth. In the era of targeted therapy aimed at the dominant molecular alteration, the implications on treatment effect and the consequences of clone selections are huge. The molecular clonal development of cancer, and especially the TRACERx and PEACE studies, were also the subject of a brilliant keynote lecture by C. Swanton. Some of it can be enjoyed by the fascinating read of “Tracking the evolution of non-small cell lung cancer” by C. Swanton and collegues in the New England Journal of Medicine 2017. I do hope the presentation will be made available as a webcast.

Why are you resisting to immune-checkpoint blockade?

M. Meyerson concluded the session by dwelling into tumour mutations that alter antigen presentation and signaling, including HLA, beta-2-microglobulin, and JAK2, major determinants of lack of response or acquired resistance to immune checkpoint inhibitors. Should we start looking for these mutations, at least in clinical trials?

A well-attended, if somewhat “tabloid-y” session was the controversy “Is there a role for second-line immunotherapy in patients with PD-L1 negative NSCLC?”. The debate was as hot as the French presidential election campaign, and both R. Herbst and B. Besse did a fine job at twisting the existing data. It does seem in the end that the question is more complex, and that PD-L1 expression alone certainly does not identify a subgroup that will benefit less from immunotherapy: we need to account for driver mutations, mutational load, among others. If you need still need a simple answer backed up by a large phase 3 trial, refer to the OAK trial, by A. Rittmeyer and colleagues in the Lancet 2016!

The forgotten ones: immune checkpoint blockade for patients with brain metastases, with EGFR or ALK positive tumours, and why you should use immunotherapy early if you can. And, are you really going to vaccinate against influenza this coming winter?

The ESMO-IASLC Best Abstracts Session yielded some interesting findings. The safety and efficacy analyses of atezolizumab in advanced NSCLC patients with or without brain metastases encompassed the PCD4989g, BIRCH, FIR, POPLAR and OAK trials. Atezolizumab was found to be safe in patients with asymptomatic and previously treated stable brain metastases. But the rather more interesting finding was the reduced risk of developing additional CNS lesions with atezolizumab compared with docetaxel. On the other hand, the time to development of CNS lesions in patients without baseline brain metastases was similar in both treatment groups. This merits further investigation, and is most certainly good news for our patients with baseline brain metastases, in whom a protective effect of immune checkpoint inhibitors is suspected. These brain metastases patients are obviously heavily selected by the stringent inclusion criteria for the OAK trial, and the real-life validity is still somewhat questionable, but the concept of the CNS as an immunological sanctuary definitely has to be accounted for.

Still in the ESMO-IASLC Best Abstracts Session, the analysis of the EGFR mutant or ALK positive cohort in the ATLANTIC ≥3rd line durvalumab study added to our understanding of the utility of immune checkpoint inhibitors in these molecular subgroups. While the data on ALK rearranged tumours are still scarce, the EGFR mutants are now adding up to a respectable dataset. The study found a 1-year overall survival (OS) of 57.4% in PD-L1 high (≥25%) patients, median OS no reached. The subgroup of EGFR/ALK+ but PD-L1 low/neg had a median OS of 9.9 months. The encouraging OS results reinforce the utility of immune checkpoint inhibitors, while the optimal sequence remains to be clarified, with a strong rationale for earlier use at least in the high PD-L1 expressors.

The impact of sequencing chemotherapy and immunotherapy was the topic of a poster discussion session. In a case control study by S. Rothschild and colleagues, the odds of achieving a partial response to salvage chemotherapy was higher in patients with prior exposure to PD-1/PD-L1 inhibitors, meriting further investigation. The same author presented a worrisome 26% incidence of severe (grade 3 or 4) immune related adverse events in patients having undergone influenza vaccination while receiving PD-1/PD-L1 inhibitors, more than double the commonly observed rates. On the bright side, serological protection was good and no short-term toxicity of the vaccination could be observed.

A great many other presentations merit to be mentioned out of the groundbreaking multidisciplinary programme of the ELCC 2017. The conference showcased the latest advances in immunotherapy and screening, new steps in the treatment of molecularly defined NSCLC and the new IASLC staging. It brought together thoracic oncology specialists worldwide in order to advance science, disseminate education and improve the practice of lung cancer treatment.