Preface Michaël Duruisseaux, MD, PhD Respiratory Department, Hôpital Louis Pradel Hospices Civiles de Lyon Cancer Institute Lyon, France

Checkpoint inhibition in non-small-cell lung cancer: expanding the range of options IMpower110: interim OS findings The randomized phase III IMpower110 trial is evaluating the PD-L1 inhibitor ate­zolizumab as first-line treatment in patients with stage IV, PD-L1–positive non-small-cell lung cancer (NSCLC) independent of tumor histology.

EGFR-positive tumors: the issue of optimal therapy across several lines FLAURA: OS with first-line osimertinib In patients with advanced, EGFR-positive NSCLC, EGFR tyrosine kinase inhibitors (TKIs) represent the frontline treatment standard. Three generations of TKIs are widely available, but the ideal sequence is currently unknown.

Frontline combinations of EGFR- and angiogenesis-targeted agents In patients with untreated EGFR-mutant tumors, it has been shown that the addition of the anti-VEGF antibody beva­cizumab to first-generation EGFR TKIs induces PFS benefits with an acceptable toxicity profile [1, 2].

Exploring synergy between anti-angiogenic drugs and immunotherapy In the setting of non-squamous advanced NSCLC without actionable driver mutations, the advent of immune checkpoint inhibitor therapy has led to the implementation of new standards. Synergistic effects can be expected from anti-angiogenic treatment.

Innovations in the setting of rare mutations: ALK, ROS1, NTRK, NRG1 BFAST: blood-based NGS as a stand-alone test Oncogene-directed treatment requires molecular testing, but, as is known, limitations related to tissue collection and tissue-based testing can represent a serious obstacle in clinical practice. Blood-based next generation sequencing (NGS) has the potential to overcome some of these limitations.

CNS disease does not preclude successful treatment Neurological symptom burden at diagnosis affects survival Brain metastases occur in approximately 35 % of patients with metastatic NSCLC and are associated with a variety of neurological symptoms, as well as poor prognosis [1]. However, little is known about the prognostic impact of the symptomatic burden of CNS lesions at the time of diagnosis.

Early-stage NSCLC: promising (neo)adjuvant approaches Stephen Liu, MD, Lombardi Comprehensive Cancer Center at Georgetown University, Washington, DC, USA

Emerging survival benefits in the small-cell setting IMpower133: updated OS results Given the dismal prognosis of patients with extensive-stage small-cell lung cancer (ES-SCLC), there is a high need of effective first-line treatment options.

Preface – ESMO 2018 Sanjay Popat, PhD, FRCP Consultant Thoracic Medical Oncologist, Royal Marsden Hospital, London, UK

Checkpoint inhibition excels in all treatment lines Neoadjuvant therapy: NEOSTAR Patients with early and locally advanced (stage I-IIIA) non–small-cell lung cancer (NSCLC) usually undergo surgery, but long-term outcomes leave much to be desired. After surgery alone, the recurrence rate is substantial at more than 50 % [1].

EGFR-mutant lung cancer: what’s new with respect to activity and resistance? Erlotinib as a neoadjuvant strategy In patients with stage IIIA-N2 NSCLC, current multimodal treatment options include definitive chemoradiotherapy, surgery followed by adjuvant chemotherapy, or neoadjuvant treatment followed by surgical resection.

Several reasons support sequencing of EGFR TKI treatment Maximilian Hochmair, MD, Respiratory Oncology Unit, Department of Respiratory and Critical Care Medicine, Otto Wagner Spital, Vienna, Austria

Potent treatment options in ALK– and MET-positive disease ALESIA: confirming findings obtained in ALEX The highly selective, CNS-active ALK inhibitor alectinib has demonstrated superiority over crizotinib in the first-line setting of ALK-positive NSCLC both in the global phase III ALEX study [1] and the phase III J-ALEX trial, which was conducted in Japanese patients [2].

Preface – ESMO 2017 David R. Gandara, MD Professor of Medicine UC Davis Comprehensive Cancer Center Sacramento, California, USA

Immunotherapy: once more at the cutting edge of progress PACIFIC: durvalumab in stage III NSCLC Approximately one third of patients with non–small-cell lung cancer (NSCLC) presents with stage III, locally advanced disease. For those with good performance status and unresectable tumours, the standard of care is platinum-based doublet chemotherapy with concurrent radiotherapy.

Immunostimulation as a promising approach in SCLC IMPULSE There is a high unmet medical need regarding extensive-disease small-cell lung cancer (SCLC) that shows poor outcomes with median OS of 9 to 11 months. First-line chemotherapy usually evokes marked responses, but responders typically experience only limited periods of disease control.

Randomised findings on CT-based follow-up after resection of early NSCLC Regarding the optimal follow-up after surgery for early-stage NSCLC, the ESMO guidelines recommend patient surveillance every six months for 2-3 years with visits including history, physical examination and preferably contrast-enhanced spiral chest CT at 12 and 24 months [1].

EGFR-mutant lung cancer: sequencing as a major topic in light of new data Long-term results with osimertinib after EGFR TKI failure The first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) erlotinib and gefitinib as well as the second-generation EGFR TKI afatinib are the recommended first-line options for patients with EGFR-mutant NSCLC [1].

Interview: “Survival is the result of multiple treatment lines” Nicolas Girard, MD, PhD Institut Curie, Institut du Thorax Curie-Montsouris, Paris, France

Reaching unprecedented outcome dimensions in malignant mesothelioma Malignant pleural mesothelioma (MPM) is a rare but aggressive cancer with poor prognosis. While combination chemotherapy with platinum and pemetrexed with or without bevacizumab is a standard in first-line treatment, no approved second-line strategies have been established to date [1].

Characteristics and outcomes for SCLC arising from transformation A low but significant proportion of EGFR-mutant adenocarcinomas transforms to SCLC at the time of acquisition of resistance to EGFR TKI therapy [1]. Moreover, cases of de novo SCLC harbouring EGFR mutations have been reported [2].

ALK-positive NSCLC: updates on crizotinib and alectinib PROFILE 1014 was the first study to define the role of the ALK inhibitor crizotinib in the first-line treatment of patients with ALK-positive lung cancer.

Rare driver mutations: BRAF- and HER2-mutant NSCLC First-line dabrafenib plus trametinib BRAF driver mutations in NSCLC are rare at 2 % [1, 2], but tumours with BRAFV600E mutations have histological features suggestive of aggressive biology [3]. When treated with platinum-based chemotherapy, these patients showed less favourable outcomes [3, 4].

Preface – ESMO 2016 Silvia Novello, MD, PhD, University of Turin, Italy Dear Colleagues, According to an estimate by the World Health Organization, 1.37 million people worldwide die of lung cancer every year. Both incidence and lung-cancer–related mortality are substantial:

Rare driver mutations: encouraging results in small patient populations As well as ALK fusion mutations and EGFR mutations, studies of the genetic profiles of patients with NSCLC have identified other mutations that might be used for additional targeted therapies. Among these, ROS1 and RET rearrangements both occur in 1 % to 2 % of patients with NSCLC.

SCLC: genomic alterations pave the way to targeted approaches Rapid growth and early development of metastatic disease are characteristic of small-cell lung cancer (SCLC), which constitutes approximately 15 % of all lung cancer cases [1]. In limited-stage disease, a cure is possible with chemoradiotherapy.

No phase III benefit with selumetinib in KRAS-mutant NSCLC Oncogenic mutations of KRAS define the largest genomic subset of NSCLC (Figure). This patient group appears to derive less clinical benefit from chemotherapy than the overall NSCLC population.

EGFR-targeted therapy: at the right time in the right patient Approximately 11 % of Caucasian patients with NSCLC have tumours that harbour EGFR mutations [1], which occur in exons 18, 19, 20 and 21 of the EGFR gene. Common mutations include exon 19 in-frame deletions and the exon 21 Leu858Arg point mutation (L858R) [2].

Targeting angiogenesis can prolong life Anders Mellemgaard, MD, PhD, Clinical Associate Professor, Department of Oncology, Herlev University Hospital, Copenhagen, Denmark

Next-generation ALK inhibitors excel after crizotinib failure ALK fusion-gene–positive lung cancer occurs in approximately 5 % of patients with advanced NSCLC [1]. The ALK inhibitor crizotinib demonstrates significant initial efficacy in patients with ALK-positive advanced NSCLC.

Immune checkpoint inhibition: the picture is slowly completing itself KEYNOTE-024: first-line, PD-L1–enriched population The anti–PD-1 antibody pembrolizumab has been approved for treatment of patients with PD-L1–expressing, advanced NSCLC. The KEYNOTE-024 study focused on the first-line comparison of pembrolizumab with platinum-doublet chemotherapy [1].