Preface – ASCO 2019 Elisabeth Quoix, MD Department of Pneumology, Hôpitaux Universitaires de Strasbourg, Strasbourg, France Recipient of the BJ Kennedy Award ASCO 2019

Early-stage NSCLC: promising (neo)adjuvant approaches The NEOSTAR trial Effective treatment options are called for in patients with resectable non-small-cell lung cancer (NSCLC), as more than half of those with stage I to III disease experience relapses [1]. Chen et al. demonstrated in their animal model that tumor PD-L1 upregulation is critical for the spread and survival of metastases [2]. Based on these considerations, several clinical trials are investigating the potential benefit

Novel first-line options and other insights in EGFR-mutant lung cancer RELAY: addition of ramucirumab Although treatment with EGFR TKIs is generally efficient in patients with EGFR-mutant lung cancer, resistance inevitably develops within 8 to 12 months of the initiation of therapy, leading to treatment failure. Therefore, there is an unmet need for options that extend the activity of EGFR-targeted therapies. Dual blockade of the VEGF and EGFR signaling pathways represents a potential

Trial updates and new biomarkers in the field of immunotherapy Long-term findings with pembrolizumab: KEYNOTE-001 KEYNOTE-001 was the first trial to demonstrate the activity of the PD-1 inhibitor pembrolizumab in patients with treatment-naïve or previously treated advanced NSCLC [1]. Notably, in this multi­cohort phase IB study, pembrolizumab showed greater activity with increasing PD-L1 tumor proportion score (TPS).

Blood-based testing in ALK-positive disease Interview: Rafał Dziadziuszko, MD, PhD, Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland Rafał Dziadziuszko, MD, PhD, Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland

Rare mutations: taking treatment one step further GEOMETRY mono-1: capmatinib in MET-dysregulated NSCLC MET exon 14 skipping mutations (MET­ex14) have been reported in 3 % to 4 % of NSCLC patients [1-3]. They confer poor prognosis and poor responses to standard therapies including immunotherapy [4-8].

Small-cell tumors: improvements in the second-line setting Lurbinectedin monotherapy Only limited therapeutic options are available for patients with relapsing small-cell lung cancer (SCLC). Topotecan is the only FDA-approved treatment for platinum-sensitive disease in the second-line setting.

Expansion of clinical trial enrollment criteria: what would we gain? Broadened vs. traditional: retrospective analysis In 2017, the American Society of Clinical Oncology and the non-profit organization Friends of Cancer Research noted in their joint statement that trial enrollment criteria should strive for inclusiveness to make trial populations more representative and to maximize generalizability of findings [1].

Preface – ASCO 2018 Bruce E. Johnson, MD President, American Society of Clinical Oncology Chief Clinical Research Officer, Dana-Farber Cancer Institute, Boston, MA, USA ASCO Translational Research Professor

PD-(L)1 inhibition alone and in combination: recent insights into immunotherapy First-line, single-agent pembrolizumab: KEYNOTE-042 Monotherapy with the anti-PD-1 monoclonal antibody pembrolizumab has significantly improved clinical endpoints compared to chemotherapy in patients with metastatic non–small-cell lung cancer (NSCLC) [1, 2].

Immune checkpoint blockade: determinants of treatment success Various clinical factors beyond PD-L1 expression have been explored as predictors of response to immune checkpoint inhibition. Specifically, analyses have associated lack of tobacco exposure with diminished responsiveness to PD-1 pathway blockade in NSCLC [1, 2].

New data on EGFR-directed TKIs across 3 generations Erlotinib plus bevacizumab EGFR TKI treatment has become a standard first-line strategy for patients with advanced, EGFR-mutation–positive NSCLC. Established agents include the first-generation drugs gefitinib and erlotinib, the second-generation agents afatinib and dacomitinib, and the third-generation TKI osimertinib.

Interview with Barbara Melosky: “The sequencing question remains” Interview: Barbara Melosky, MD, FRCPC, University of British Columbia and British Columbia Cancer Agency, Vancouver, Canada

ALK-positive disease: pushing the borders of treatability CNS and non-CNS efficacy of alectinib confirmed in ALEX Standard treatment for patients with ALK-positive, advanced NSCLC includes the first-generation ALK inhibitor crizotinib and, more recently, second-generation ALK TKIs such as ceritinib and alectinib.

Recent benchmarks in the management of small-cell tumours KEYNOTE-158 Extensive-disease small-cell lung cancer (ED-SCLC) is highly responsive to first-line therapy, but early relapses commonly occur, and prognosis is poor. To date, no biomarker-driven therapies have been established.

Comprehensive sequencing of plasma cell-free DNA permits non-invasive cancer detection Early detection of lung cancer is a highly unmet medical need. Even though low-dose computed tomography (LDCT) has been shown to improve lung cancer mortality in high-risk individuals [1], the rate of clinical adoption remains low at 1.9 % [2, 3].

Distinct somatic genome variations in young lung cancer patients Lung cancer in young adults is relatively rare, but it is considered a unique subgroup with distinct biology [1]. In patients aged ≤ 40 years, the incidence of lung cancer has been found to be 4 % [2], and in those aged ≤ 45 years, 5.3 % [3].

Preface – ASCO 2017 Anna Nowak, MBBS FRACP PhD

EGFR-targeted treatments: insights from the adjuvant to the resistant setting Gefitinib after complete resection Approximately 20 % to 25 % of non–small-cell lung cancer (NSCLC) patients are eligible for surgical resection with curative intent [1]. To date, cisplatin-based chemotherapy constitutes the adjuvant standard of care for patients with stage II-IIIA completely resected NSCLC.

New standards of care for ALK-positive disease The first-generation ALK inhibitor  crizotinib is the current standard option  for patients with newly diagnosed,  advanced ALK-positive NSCLC.  However, patients invariably relapse on  crizotinib treatment, with the central  nervous system (CNS) being one of the  most common and challenging sites of  relapse.

Reducing the danger that arises from the CNS as a site of progression Brain metastases and leptomeningeal disease represent major clinical challenges in the management of patients with NSCLC. They are generally associated with poor prognosis, and their treatment is difficult due to the paucity of effective therapeutic options.

Diagnostics of EGFR-mutant disease: biomarkers with significant clinical implications Alterations in multiple oncogenic pathways drive progression The clinical relevance of additional genetic alterations in advanced EGFR-mutant NSCLC is not clear. Blakely et al. hypothesised that co-occurring genomic alterations in cancer-related genes can cooperate with the mutant EGFR to drive de-novo resistance to EGFR TKI treatments [1].

Established targeted agents taking root in the HER2-positive setting HER2 aberrations in lung cancer are being increasingly identified due to the use of sensitive testing procedures, such as multiplexed testing and next-generation sequencing. Mutations of the HER2 gene need to be distinguished from HER2 amplifications and HER2 protein overexpression.

Further defining the optimal use of immune checkpoint inhibitors Neoadjuvant evaluation of nivolumab As the anti-PD-1 antibody nivolumab is known to induce deep and durable responses in a subset of lung cancer patients, this agent was investigated in the neoadjuvant setting, which is an area of unmet need. There have been no advances in systemic treatment of resectable lung cancer since 2004.

Real-world utility of ctDNA NGS to identify matched targeted therapy Liquid biopsy for plasma circulating tumour DNA (ctDNA) next generation sequencing (NGS) is a rapidly evolving science. Plasma ctDNA assays are now commercially available, and are increasingly adopted in the community with a paucity of evidence-based guidance on timing and value of this test.

Lung cancer in China: hurdles and progress Yi-Long Wu, MD Guangdon Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China

Anti-angiogenic and immunotherapeutic approaches in mesothelioma The LUME-Meso trial Malignant pleural mesothelioma (MPM) is a rare tumour that is often diagnosed at an advanced stage. Limited efficacy of the available therapies contributes to the generally poor prognosis for MPM patients.

Enhancing the profile of KRAS-mutant lung cancer Characteristics and outcomes KRAS mutations constitute the largest subset of oncogene-driven lung adenocarcinomas, at approximately 30 %. Patients with KRAS-mutant metastatic lung cancer have heterogeneous clinical outcomes depending on the mutation subtype and associated co-mutations.

Preface – ASCO 2016 Paul A. Bunn Jr., MD, FASCO, Distinguished Professor and James Dudley Chair of Lung Cancer Research, University of Colorado Cancer Center, Aurora, Colorado, USA. 2016 David A. Karnofsky Memorial Award Winner

Immunotherapy: updates on clinical trials and other insights Nivolumab plus ipilimumab: CheckMate 012 Besides targeted drugs for driver mutations, immunotherapies represent one of the two recent major advancements of the past decade for the treatment of metastatic non–small-cell lung cancer (NSCLC).

Expanding treatment options in NSCLC patients with rare mutations: ALK, ROS1, MET, BRAF ALK gene rearrangements occur in approximately 4 %to 5 % of all Caucasian and Asian patients with advanced NSCLC. Crizotinib was the first approved ALK inhibitor and is the current front-line standard treatment for ALK-positive NSCLC.

Lung cancer care in Latin America: evolution of modern therapies and challenges to overcome the existing gaps Gustavo Werutsky, MD, Latin American Cooperative Oncology Group, Hospital São Lucas PUCRS University, Porto Alegre, Brazil

Exploring established and novel EGFR-directed agents PROs & dose modifications in LUX-Lung 7 The phase IIb LUX-Lung 7 trial was a head-to-head comparison of the second- generation ErbB family blocker afatinib and the first-generation reversible EGFR TKI gefitinib in patients with treatment-naïve, EGFR-mutation-positive, advanced (stage IIIB/IV) adenocarcinoma of the lung.

“The importance of first-line and second-line targeted agents is obvious” Nir Peled MD, PhD, FCCP, Head of the Thoracic Cancer Unit, Thoracic Cancer Service, Davidoff Cancer Center, Petah Tikva, Israel

Mutational analysis: on the road to refined standards LCMC II The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional consortium for the study of driver mutations of lung adenocarcinoma.

New approaches are raising hope for SCLC patients Only minor progress has been made over the past 30 to 40 years in the treatment of small-cell lung cancer (SCLC), which accounts for 10 % to 15 % of lung cancer cases. SCLC is radiosensitive, but approximately 70 % of patients present with extended disease that cannot be included within one radiotherapy field.

ULTIMATE: chemotherapy plus bevacizumab beyond first line As chemotherapy in the second-line or third-line settings of NSCLC shows limited efficacy, the phase III, randomised ULTIMATE trial tested the combination of chemotherapy and bevacizumab in patients with advanced NSCLC of non-squamous histology, who had progressed after one or two lines of treatment.

Locally advanced NSCLC: oral vinorelbine shows better safety profile than etoposide The randomised, multicentre, open-label, phase II RENO trial was conducted with the objective of establishing a standard chemotherapy regimen in the setting of chemo-radiotherapy of locally advanced NSCLC.

PFS improvement due to local therapy in oligometastatic NSCLC Evidence suggests the existence of a ,limited metastatic’ NSCLC phenotype. However, the type of optimal treatment and the role of aggressive local therapy in these patients remain controversial. Gomez et al. presented the first prospective, randomised trial to address this question.

Similar outcomes obtained with four adjuvant cisplatin-based chemotherapy regimens The phase III E1505 trial was designed to investigate the addition of bevacizumab to adjuvant chemotherapy in patients with early-stage, completely resected NSCLC. It was based on the rationale that the benefit of adjuvant cisplatin-based chemotherapy is modest in this population.

Preface – ASCO 2015 Dear Colleagues, As for many other oncological diseases, the management of lung cancer has undergone major changes in the last few years with the rise of targeted therapies, and more lately, of immunotherapy.

Metastatic NSCLC: new drugs and updates in well-known agents Squamous-cell carcinoma: nedaplatin Tumours with squamous histology account for 20 % to 30 % of cases of non–small-cell lung cancer (NSCLC).

Interview: “EGFR testing is a reality in European countries” Robert Pirker, MD, Medical University of Vienna, Vienna, Austria

Immunotherapy: effective treatments gathering on the horizon EGFR mutations and ALK rearrangements are well-established therapeutic targets in NSCLC, with EGFR TKIs and ALK TKIs representing the first-line standard of care for these molecular subsets of patients.

Statement: “Select the patients who will be able to benefit” Alex A. Adjei, MD, PhD, FACP, Roswell Park Cancer Institute, New York, USA

Novel approaches in small-cell lung cancer Small-cell lung cancer (SCLC) accounts for approximately 15 % of all lung cancers, and it is associated with poor outcomes [1]. 70 % of these patients present with extensive disease. Their treatment remains a significant challenge for oncologists.

Further analyses of biomarkers Immune checkpoint inhibitors have become established as standard therapy for certain subsets of NSCLC patients.

Interview: “These findings will change the standard-of-care” Interview: Barbara Melosky, MD, FRCPC, University of British Columbia and British Columbia Cancer Agency, Vancouver, Canada Will findings presented here at ASCO change the future of NSCLC therapy? This year’s ASCO Congress was very interesting. The findings will definitely change the standard-of-care in non–small-cell and small-cell carcinoma.

Phase III results in local and regional lung cancer PROCLAIM: chemoradiotherapy followed by pemetrexed consolidation The standard-of-care for inoperable stage III NSCLC is concurrent chemoradiotherapy. However, the role of consolidation chemotherapy remains controversial.