ROS proto-oncogene 1 (ROS1) rearrangements are reported in about 1–2% of non-squamous non-small-cell lung cancer (NSCLC). After efficacy of crizotinib was demonstrated, identification of ROS1 translocations in advanced disease became fundamental to give patients the chance of specific and effective treatment. Different methods are available for detection of rearrangements, and probably the real prevalence of ROS1 rearrangements is higher than that reported in literature, as our capacity to detect gene rearrangements is improving. In particular, with next generation sequencing (NGS) techniques, we are currently able to assess multiple genes simultaneously with increasing sensitivity. This is leading to overcome the “single oncogenic driver” paradigm, and in the very near future, the co-existence of multiple drivers will probably emerge more frequently and represent a therapeutic issue. Since recently, crizotinib has been the only available therapy, but today, many other tyrosine kinase inhibitors (TKI) are emerging and seem promising both in first and subsequent lines of treatment. Indeed, novel inhibitors are also able to overcome resistance mutations to crizotinib, hypothesizing a possible sequential strategy also in ROS1-rearranged disease. In this review, we will focus on ROS1 rearrangements, dealing with diagnostic aspects, new therapeutic options, resistance issues and the coexistence of ROS1 translocations with other molecular alterations.

Lung cancer (LC) is the leading cause of cancer mortality worldwide. Despite current therapies, including surgery, radiotherapy, targeted therapies, and immunotherapy, most patients experience relapse. Immune checkpoint inhibitors (ICIs) have revolutionized LC treatment, but only a subset of patients benefit from them. Chimeric antigen receptor (CAR) T cell therapy emerges as an innovative and promising strategy in oncology. CAR T cells are genetically modified T lymphocytes that express a chimeric receptor specific for a tumor antigen. Very promising in hematology, CAR T has so far struggled to be transferred into the clinic for solid tumors, including LC. CAR T strategy against LC presents challenges in the selection of the optimal antigen to avoid off-target effects, for the known antigen heterogeneity and immunosuppressive environment of LC and the relatively short persistence of CAR T that may encounter disseminated diseases. Despite these limitations, here we describe growing preclinical and clinical studies that are exploring various LC antigens for CAR T within a variety of novel approaches and combinatorial strategies to overcome the barriers. Considering this emerging critical mass and despite the limits, we expect this endeavour to translate a fraction CAR T into clinical practice with efficacy against the still deadly LCs.

Small cell lung cancer (SCLC) is a highly aggressive malignancy that accounts for about 14% of all lung cancers. Platinum-based chemotherapy has been the only available treatment for a long time, until the introduction of immune checkpoint inhibitors (ICIs) recently changed first-line standard of care and shed light on the pivotal role of the immune system. Despite improved survival in a subset of patients, a lot of them still do not benefit from first-line chemo-immunotherapy, and several studies are investigating whether different combination strategies (with both systemic and local treatments, such as radiotherapy) may improve patient outcomes. Moreover, research of biomarkers that may be used to predict patients’ outcomes is ongoing. In addition to ICIs, immunotherapy offers other different strategies, including naked monoclonal antibodies targeting tumor associated antigens, conjugated antibody, bispecific antibodies and cellular therapies. In this review, we summarize the main evidence available about the use of immunotherapy in SCLC, the rationale behind combination strategies and the studies that are currently ongoing in this setting, in order to give the reader a clear and complete view of this rapidly expanding topic.

Plain language summary Aims of the study were to explore outcomes and toxicities of chemotherapy-immunotherapy (CT-IT) for patients (pts) with metastatic nonsquamous NSCLC (mNSCLC) in a real practice experience, because practice experience not always could be the same of experimental experience. We collected clinical data of 26 pts with mNSCLC, treated with CT-IT at our Institution from January 2020 to January 2021. We observed efficacy and tolerability of treatment were similar to known data, except for thyroid disfunctions (ThD) that was more frequent in our experience. This collateral effect was not cause of treatment interruption, indeed the pts with this manifestation would seem responder better to this therapy. However, we need more time and kind of studies for confirm this observation. Introduction: Aims of the study were to explore outcomes and toxicities of chemotherapy-immunotherapy (CT-IT) for patients (pts) with metastatic nonsquamous non-small-cell lung cancer (mNSCLC) in a real-world population. Materials & methods: Clinical data of 26 pts with mNSCLC treated with CT-IT at our institution from January 2020 to January 2021 were collected retrospectively. Results: Median follow-up time was 7.7 months. Median progression-free survival was 9.5 months. The most frequent immune-related adverse event was thyroid dysfunction (ThD): 30.7%. Conclusion: There was a higher rate of ThD in this study population compared with the literature, with a possible correlation with clinical outcomes.