Background: CameL phase 3 study demonstrated the superiority of camrelizumab plus chemotherapy over chemotherapy alone for progression-free survival in patients with previously untreated advanced non-squamous non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations. Here, we present the 5-year outcomes. Methods: Patients were randomized (1:1) and received 4–6 cycles of camrelizumab plus carboplatin and pemetrexed (n=205) or carboplatin and pemetrexed (n=207) every 3 weeks, followed by maintenance camrelizumab plus pemetrexed or pemetrexed only. Crossover from chemotherapy group to camrelizumab monotherapy was permitted after disease progression. Results: Median time from randomization to data cut-off was 65.2 months (range, 59.7–72.2). HR for overall survival (OS) was 0.74 (95% CI 0.58 to 0.93; one-sided p=0.0043), and was 0.62 (95% CI 0.49 to 0.79; one-sided p<0.0001) after adjustment for crossover. Five-year OS rates were 31.2% (95% CI 24.7% to 37.9%) with camrelizumab plus chemotherapy versus 19.3% (95% CI 13.9% to 25.3%) with chemotherapy alone. Among the 33 patients who completed 2 years of camrelizumab, 5-year OS rate was 84.3% (95% CI 66.4% to 93.2%), and 5-year duration of response rate was 46.5% (95% CI 24.9% to 65.6%) in the 32 responders. No new safety signals were noted. Conclusions: Camrelizumab plus carboplatin and pemetrexed as first-line therapy continued to demonstrate long-term OS benefit over carboplatin and pemetrexed, with manageable toxicity. Patients who completed 2 years of camrelizumab had enduring response and impressive OS. Current 5-year updated analysis further supports camrelizumab plus carboplatin and pemetrexed as a standard-of-care for previously untreated advanced non-squamous NSCLC without EGFR/ALK alterations. Trial registration number: NCT03134872.

Platinum-based chemotherapy improves survival among patients with non-small cell lung cancer (NSCLC), but the efficiency is limited due to resistance. In this study, we aimed to identify the expression of Aurora-A and its correlation with cisplatin resistance and prognosis in NSCLC.

Thoracic radiotherapy increases the risk of radiation‑induced heart damage (RIHD); however, the molecular mechanisms underlying these changes are not fully understood. The aim of the present study was to investigate the effects of radiation on the mouse heart using high‑throughput proteomics. Male C57BL/6J mice were used to establish a model of RIHD by exposing the entire heart to 16 Gy high‑energy X‑rays, and cardiac injuries were verified using a cardiac echocardiogram, as well as by measuring serum brain natriuretic peptide levels and conducting H&E and Masson staining 5 months after irradiation. Proteomics experiments were performed using the heart apex of 5‑month irradiated mice and control mice that underwent sham‑irradiation. The most significantly differentially expressed proteins were enriched in 'cardiac fibrosis' and 'energy metabolism'. Next, the cardiac fibrosis and changes to energy metabolism were confirmed using immunohistochemistry staining and western blotting. Extracellular matrix proteins, such as collagen type 1 α 1 chain, collagen type III α 1 chain, vimentin and CCCTC‑binding factor, along with metabolism‑related proteins, such as fatty acid synthase and solute carrier family 25 member 1, exhibited upregulated expression following exposure to ionizing radiation. Additionally, the myocardial mitochondria inner membranes were injured, along with a decrease in ATP levels and the accumulation of lactic acid in the irradiated heart tissues. These results suggest that the high doses of ionizing radiation used lead to structural remodeling, functional injury and fibrotic alterations in the mouse heart. Radiation‑induced mitochondrial damage and metabolic alterations of the cardiac tissue may thus be a pathogenic mechanism of RIHD.

Background: Leptomeningeal metastasis (LM) is associated with poor prognosis in non‐small cell lung cancer (NSCLC). The aim of this study was to investigate the efficacy and safety of osimertinib combined with bevacizumab for LM from epidermal growth factor receptor mutation (EGFRm) NSCLC.Methods: We conducted a phase II single‐arm prospective clinical trial of EGFRm NSCLC with LM treated with osimertinib combined with bevacizumab. LM response assessment was based on the modified RANO LM radiological criteria; CNS and extra‐CNS response was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The primary end points included LM progression‐free survival (PFS) and objective response rate (ORR); the secondary end points included safety and LM overall survival (OS).Results: A total of 14 patients were included in the study, with a median age of 61 years, and they were predominantly female (64%). EGFR mutations were reported in exons 19 del (n = 7) and 21 L858R (n = 7). When LM was diagnosed, 12 (85.7%) patients had clinical symptoms, 71.4% (10/14) of patients were diagnosed with LM by cytology, and five (35.7%) patients had a performance status (PS) score > 2. The median LM PFS was 9.3 months (95% CI: 8.2–10.4), and the LM ORR was 50%. The safety findings in the present study were consistent with the known profile of osimertinib with bevacizumab; the median LM OS was 12.6 months, and the one‐year survival rate was 35.7%.Conclusions: Osimertinib combined with bevacizumab is an appropriate treatment option for patients with LM from EGFRm NSCLC.Key points: Significant findings of the study: To date, there is no prospective clinical study on the treatment of osimertinib combined with bevacizumab in EGFRm NSCLC with LM.What this study adds: The median LM PFS was 9.3 months (95% CI: 8.2–10.4), and the LM ORR was 50%, the median LM OS was 12.6 months, and the one‐year survival rate was 35.7%. Osimertinib combined with bevacizumab is an appropriate treatment option for patients with LM from EGFRm NSCLC.

Background: Although arrhythmias have been reported in patients treated with immune checkpoint inhibitors (ICIs), the association between arrhythmias and ICIs has not been thoroughly evaluated in real‐world studies. We aimed to describe the major features of ICI‐related arrhythmic events and identify the factors that contributed to death.Methods: A disproportionality analysis was performed using data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 2011 to December 2021. Reporting odds ratios (RORs), proportional reporting ratio and information component were used to assess whether adverse arrhythmic events were associated with ICIs. The clinical characteristics of patients with ICI‐associated arrhythmias were compared with fatal and non‐fatal arrhythmias. The time to onset (TTO), fatality rates of arrhythmic events were also investigated.Results: We identified a total of 1945 cases of ICI‐related arrhythmic events. Men (64.78%) were identified significantly more frequently than women (28.84%). The median age was 68 years ([interquartile range, IQR] 60–75 years). Anti‐programmed cell death‐1 (PD‐1) and anti‐programmed cell death ligand‐1 (PD‐L1) were associated with adverse arrhythmic events, corresponding to ROR 1.11 (95% confidence interval [CI] 1.05–1.17) and ROR 1.34 (95% CI 1.20–1.49), respectively. However, anti‐cytotoxic T‐lymphocyte associated protein 4 or combination immunotherapy did not appear to be associated with arrhythmic events. Atrial fibrillation (N = 576, 0.62%), cardiac arrest (N = 284, 0.31%), tachycardia (N = 175, 0.19%) were the most common adverse arrhythmic events. Sudden death and complete atrioventricular block are adverse events that are significantly associated with ICI‐related arrhythmic events and have strong signal intensity. The TTO of cases that resulted in death (30 days [IQR] 11–73.75) was significantly earlier than that of cases that did not result in death (33 days [IQR 10.5–88.5], p = 0.003). ICI‐related arrhythmic events were severe with death occurring in 507 (26.07%) of 1945 arrhythmias cases.Conclusions: Treatment with PD‐1/PD‐L1 may cause arrhythmic events, which are severe and tend to occur early on during treatment. It is important to identify ICI‐related arrhythmias as early as possible, and to manage them appropriately.