Lung cancer : journal of the International Association for the Study of Lung Cancer
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Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 80-85% of cases. Epidermal growth factor receptor (EGFR) mutations are observed in approximately 40% and 20% of patients with NSCLC in Asian and non-Asian populations, respectively. First-generation (gefitinib, erlotinib) and second-generation (afatinib, dacomitinib) EGFR-tyrosine kinase inhibitors (TKIs) have been standard-of-care (SoC) first-line treatment for patients with sensitizing EGFR mutation positive advanced NSCLC following Phase III trials versus platinum-based doublet chemotherapy. ⋯ The second-generation EGFR-TKI dacomitinib has also recently been approved for the first-line treatment of EGFRm positive metastatic NSCLC. There remains a need to determine appropriate sequencing of EGFR-TKIs in this setting, including EGFR-TKIs as monotherapy or in combination with other TKIs / signaling pathway inhibitors. This review considers the evolving role of sequencing treatments to maximize benefits for patients with EGFRm positive advanced NSCLC.
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Despite the highly immunogenic potential of small cell lung cancer (SCLC), progress in evaluating the therapeutic value of immune checkpoint agents has lagged behind that of non-small cell lung cancer. Results from a number of phase I-III clinical trials that specifically address the use of anti-PD-1, anti-PD-L1 and anti-CTLA-4 agents in SCLC have now been reported. This review will focus on the available evidence for immune checkpoint blockade in SCLC and review current biomarker strategies with the aim of providing perspective and interpretation of this data for clinical practice.
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Lung cancer screening with low-dose CT (LDCT) is already available in certain parts of the world, such as the United States, but not yet in Europe. The recently published European position statement on lung cancer screening has recommended planning for implementation of screening to start within 18-months [1]. Pilot European programmes are already underway, primarily in the United Kingdom (UK), delivering lung cancer screening to their local populations. This review article acknowledges the evidence base for LDCT screening and will discuss the challenges that still need to be overcome in an attempt to answer the question: are we ready to implement in Europe?
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This network meta-analysis (NMA), based on 12 phase-III studies with 9,236 metastatic NSCLC patients, aims to compare the efficacy of treatments including at least one immune-checkpoint inhibitor (ICI) with or without chemotherapy, as frontline therapy for advanced NSCLC patients. The NMA includes direct randomized evidence on treatments of interest along with indirect evidence from randomized studies with chemotherapy as the common comparator. Studies were identified by searching PubMed, and the abstracts of most recent main oncology congresses. ⋯ Of note, ABC is evaluated only for OS in non-squamous patients while the pembrolizumab-monotherapy PFS benefit and the atezolizumab/chemotherapy OS benefit are probably under-estimated since most of the data stems from non-significant interim analyses of ongoing studies [KN042;IM131/132/150]. In conclusion, the addition of chemotherapy to ICIs enhanced their treatment efficacy as first-line treatment for advanced NSCLC patients. The combination of chemotherapy with either pembrolizumab or atezolizumab show consistently higher efficacy than chemotherapy-alone or any other ICI-combination or monotherapy, particularly in non-squamous patients.
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The incidence of CNS metastasis at the time of diagnosis of and during the natural disease history of advanced ROS1+ NSCLC is largely unknown. It is generally believed that the incidence of CNS metastasis is lower in ROS1+ NSCLC than ALK+ NSCLC as ROS1 fusions are regarded as a less powerful driver mutation than ALK fusions in ALK+ NSCLC based on the longer progression-free survival of ROS1+ NSCLC patients than ALK+ NSCLC patients treated with crizotinib. Here we reviewed the incidence of CNS metastasis from prospective clinical trials and retrospective case series from primarily single institution. ⋯ We reviewed reported intra-cranial activity of all preclinical and clinical development stage ROS1 TKIs and pemetrexed-based chemotherapy in ROS1+ NSCLC patients. While several ROS1 TKIs (i.e. entrectinib, cabozantinib, lorlatinib, repotrectinib) have reported intra-cranial response rates, there is no literature reporting on the intra-cranial activity of pemetrexed-based chemotherapy in ROS1+ NSCLC patients. In summary, better understanding the high incidence of CNS metastasis in ROS1+ NSCLC patients, how certain ROS1 fusion variant may increase the incidence of CNS metastasis, and any intra-cranial efficacy data of pemetrexed in ROS1+ NSCLC are all urgently needed.