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Introduction: Small cell lung cancer (SCLC) is an aggressive tumor with a severe prognosis. At the time of diagnosis, most patients present with extensive-stage (ES) disease. For decades, platinum-based chemotherapy has been the only pillar of SCLC treatment, but now, the clinical management of this disease is rapidly evolving thanks to the introduction of immune checkpoint inhibitors (ICIs)., Areas Covered: In this review, we describe the most recent advances in the treatment of SCLC and discuss the emerging challenges associated with ICI treatments. Meaningful data were collected from the currently available literature on PubMed and in international oncology meetings., Expert Opinion: Recently, meaningful improvements in outcomes of SCLC patients have been achieved with anti-PD-L1 atezolizumab or durvalumab combined with chemotherapy in first line. Results of studies evaluating the role of ICIs in limited-stage (LS) SCLC patients are awaited. Further efforts are required to better understand the role of immunotherapy in the treatment of SCLC and to identify patients most likely to benefit from this treatment strategy.

Introduction : The discovery of new actionable oncogenic drivers has led to the development of effective antineoplastic targeted agents in advanced non-small cell lung cancer (NSCLC). While the role of inhibitors of the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) is widely acknowledged, other oncogenic drivers can be exploited as therapeutic targets. Areas covered : Our aim is to explore the therapeutic role of actionable oncogenic drivers, including well-established targets, such as EGFR, ALK, and ROS1, as well as less frequent drivers for which specific agents are at different stages of clinical development, such as MET, RET, BRAF, and NTRK. Expert opinion : Targeted agents have revolutionized the management of advanced NSCLC; in particular, novel agents and combinations targeting EGFR, ALK, ROS1, BRAF, and NTRK have become available and others are on their way. The molecularly driven approach to advanced NSCLC requires adequate tumor samples, as well as increasingly complex technologies designed to assess multiple targets on limited available tissue in an acceptable time-span. Furthermore, the role of other novel antineoplastic approaches, such as immunotherapy with immune checkpoint inhibitors, needs to be elucidated in the case of patients with oncogenic-driven NSCLC.

Introduction: Lung cancer represents the most common cause of cancer death worldwide. While the prognosis remains poor, immunotherapy is giving a positive impact on survival. Cancer vaccines represent a form of active immunotherapy that historically has given modest results in terms of efficacy. The overexpression of the EGFR by tumor cells was reported in more than half of cases of lung cancer, representing a mechanism of cancerogenesis. CIMAvax-EGF, a therapeutic vaccine for non-small cell lung cancer (NSCLC) developed in Cuba, consists of a human recombinant EGF able to induce antibodies against the autologous EGF, resulting in serum EGF withdrawal and lower EGF-EGFR interaction. Area covered: We critically reviewed the existing literature about CIMAvax-EGF, from the Pilot studies to the efficacy controlled studies. We also overviewed the ongoing trials. Expert opinion: CIMAvax-EGF demonstrated to be safe and immunogenic. In a phase III randomized study CIMAvax-EGF, used as a switch maintenance treatment after platinum-based chemotherapy, did not significantly improve survival. Current data are not sufficient to recommend CIMAvax-EGF as a treatment option for advanced stage NSCLC. Further studies, conducted in a context of worldwide standardized clinical practice, are needed to better define if a subpopulation of patients can benefit from the vaccination.

Introduction: Fibroblast growth factor receptor (FGFR) due to its central role in regulating cell survival, is a promising target for cancer therapeutics. Dysregulation of the FGFR pathway has been observed in several malignancies, including non-small cell lung cancer (NSCLC) particularly in patients with squamous histology. Areas covered: The aim of this article is to review the most relevant findings of clinical trials investigating drugs targeting FGFR pathway: such as FGFR tyrosine kinase inhibitors (TKIs), FGFR monoclonal antibodies and FGF ligand traps in NSCLC patients. Expert opinion: At present, clinical activity of drugs targeting FGFR in NSCLC is disappointing. Further studies are needed in order to better identify patients who might benefit from these drugs and to clarify the mechanisms of resistance to these compounds.

Introduction: Immune check-point inhibitors are now employed as single-agents in current practice for the treatment of advanced non-small cell lung cancer (NSCLC), while combinations of different inhibitors are being evaluated in clinical trials. Although the safety profile of these compounds, with particular reference to drugs targeting programmed death protein 1 (PD-1) and its ligand (PD-L1), is generally considered manageable, peculiar, immune-related toxicities may onset. Areas covered: This review focuses on the immune-related adverse events (irAEs) observed during immune check-point blockade in NSCLC and their management. The authors report the incidence of irAEs based on the currently available data involving NSCLC and provide recommendations on the general approach to irAEs, as well as indications for the most relevant site-specific events. Expert opinion: Since irAEs may involve a wide range of organs and systems and are potentially reversible if promptly treated, early diagnosis should always be achieved; this might be particularly challenging when other potential causes of toxicity are suspected, such as infections or concurrent treatments. Finally, drugs active on the PD-1/PD-L1 axis appear to be generally manageable even when they are administered to patients with relevant comorbidities, provided that adequate clinical monitoring is performed.

Introduction: Vinflunine belongs to the class of vinca alkaloids and acts by disrupting the microtubule dynamics during cell cycle; this agent is currently available for previously treated advanced transitional cell carcinoma in Europe. The aim of this invited review is to evaluate the potential role of vinflunine for the treatment of non-small cell lung cancer (NSCLC). Areas covered: The potential role of vinflunine in NSCLC is discussed on the basis of the available data, including full papers and meeting abstracts. Relevant preclinical studies describing the pharmacological properties of vinflunine are also included. The review also summarizes clinical studies, including phase I trials involving NSCLC among other tumors as well as phase II/III trials specifically addressing this malignancy. Additionally, the safety profile and the current regulatory status of vinflunine is discussed. Expert opinion: Vinflunine is active as single agent and as part of platinum-based combinations in NSCLC. It results non-inferior to docetaxel in a randomized phase III trial including previously treated NSCLC patients; additionally, its safety profile is generally considered manageable. Ultimately, further studies are needed to confirm the role of vinflunine in NSCLC, in consideration of the evolving evidence regarding targeted therapies and immune check-point inhibitors.

Introduction: Immunotherapy has become a promising approach for the treatment of NSCLC. In order to stimulate the host immune system against tumour antigens, several cancer vaccines have been generated and evaluated. Belagenpumatucel-L is a whole tumour cell vaccine expressing the antisense strand of the TGF-β2 gene., Areas Covered: The purpose of this article is to review the most relevant findings of clinical trials testing belagenpumatucel-L in advanced NSCLC patients., Expert Opinion: Although the Phase III trial investigating belagenpumatucel-L in stage III/IV patients did not meet its primary end point, a survival benefit was observed in several subgroups of patients. Further studies are needed in order to select patients who may benefit from this vaccine.

Introduction: Despite recent advances with new chemotherapeutic agents and target therapies, the prognosis of NSCLC remains poor. Recent results from clinical trials of immunotherapeutic agents, especially with immune checkpoint inhibitors, make this approach very exciting in NSCLC. Ipilimumab is a monoclonal antibody directed against cytotoxic T-lymphocyte antigen 4 that is able to stimulate the antitumour immune response by promoting T-cell activation., Areas Covered: We have reviewed the literature and have described the most important results obtained with ipilimumab in NSCLC in recent trials with a specific focus on its peculiar toxicity profile and pattern of response. Trials ongoing with ipilimumab are also reported., Expert Opinion: The results from clinical trials with ipilimumab are promising. Some important issues in the near future will be to identify prognostic and predictive biomarkers to select patients who could benefit from this drug. Further studies are warranted to understand how to combine ipilimumab with other anticancer strategies.