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. El Osta et al. analysed the Lung Cancer Mutation Consortium (LCMC) database to evaluate the characteristics of these patients and the effect of KRAS mutation features on their outcomes.
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. Since 2003, the only approved regimen for MPM treatment has been chemotherapy with pemetrexed and cisplatin, with median survival of approximately 12 months.
Lung cancer is a considerable issue in China. Every year, we have 700,000 new cases. There is a need to perform clinical trials and to launch innovative drugs. With regard to the introduction of targeted therapies, China lags 3 to 4 years behind when compared to the western countries. Two months ago, the EGFR TKI afatinib was launched, offering Chinese patients with EGFR-mutant lung cancer an effective treatment option.
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. Sabari et al. sought to determine the feasibility and utility of plasma ctDNA NGS to identify matched targeted therapy in a real-world clinical setting.
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. Chaft et al. hypothesised that neoadjuvant nivolumab treatment might induce immunity against micrometastases.
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. In contrast to breast and gastric cancer, HER2 overexpression in NSCLC does not always occur with HER2 amplification, while amplifications and HER2 mutations are generally mutually exclusive.
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. The investigators performed targeted exome sequencing of plasma cell-free DNA (cfDNA) in 86 samples collected from 81 patients with known clinical history.
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. Moreover, patients with CNS lesions are frequently excluded from clinical trials. Progress in this area is therefore slow, and more treatments are urgently needed.
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. The second-generation ALK inhibitor alectinib is more potent than crizotinib and shows clinical activity in crizotinib-resistant NSCLC.
Approximately 20 % to 25 % of non–small-cell lung cancer (NSCLC) patients are eligible for surgical resection with curative intent. To date, cisplatin-based chemotherapy constitutes the adjuvant standard of care for patients with stage II-IIIA completely resected NSCLC. The first-generation EGFR tyrosine kinase inhibitor (TKI) gefitinib is used as standard first-line treatment in patients with advanced EGFR-mutant NSCLC.
