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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

Abstract Background Immune checkpoint inhibitors (ICIs) are the standard treatment for advanced lung cancer, but immune‐related adverse events (irAEs) remain poorly understood, especially in a real‐world setting. Methods A multicenter observational study was conducted. Medical records of lung cancer patients treated with ICIs at 26 hospitals from January 1, 2015, to February 28, 2021, were retrieved. Types of ICIs included antiprogrammed cell death 1 or antiprogrammed cell death ligand 1 (PD‐L1) monotherapy, anticytotoxic T‐lymphocyte antigen‐4 monotherapy, or combination therapy. Results In total, 1905 patients with advanced lung cancer were evaluated. The median age was 63 (range 28–87) years, and the male/female ratio was 3.1:1 (1442/463). The primary histological subtype was adenocarcinoma (915). A total of 26.9% (512/1905) of the patients developed 671 irAEs, and 5.8% (110/1905) developed 120 grade 3–5 irAEs. Median duration from ICI initiation to irAEs onset was 56 (range 0–1160) days. The most common irAEs were thyroid dysfunction (7.2%, 138/1905), pneumonitis (6.5%, 124/1905), and dermatological toxicities (6.0%, 115/1905). A total of 162 irAEs were treated with steroids and 11 irAEs led to death. Patients with positive PD‐L1 expression (≥1%) and who received first‐line ICI treatment developed more irAEs. Patients who developed irAEs had a better disease control rate (DCR, 71.3% [365/512] vs. 56.0% [780/1145]; p

Background Almost all cells are capable of secreting exosomes (Exos) for intercellular communication and regulation. Therefore, Exos can be used as a natural therapeutic platform to regulate genes or deliver drugs to treat diseases. M1 macrophages inhibit tumor growth by releasing pro-inflammatory factors. This study explored the applicability of M1 macrophage exosomes (M1-Exos) as gene carriers and the effects on GNG5 protein, and further examined whether macrophage repolarization could inhibit tumor activity. Methods M0 macrophages were polarized toward M1 using vitexin. Exos were obtained from M1 macrophages by ultra-centrifugation. The transwell non-contact co-culture system was used to co-culture M1 macrophages with HLF-α human lung epithelial cells or A549 or H1299 lung cancer cells. MTT, scratch, and transwell assays were used to detect the cell viability, migration, and invasion ability of cells in the four groups. Flow cytometry was used to detect the apoptosis rate of each group, and western blot (WB) analysis was performed to detect the change in the expression of proliferation- and apoptosis-related proteins. We screened the differentially expressed microRNAs using quantitative polymerase chain reaction technology. Luciferase reporter analysis was performed to explore the interaction between miRNA and protein. We used Xenografted A549 tumors in nude mice to study the effect of M1-Exos on tumor cell growth in vivo. Results The results showed that, under the M1 macrophage co-culture system, lung cancer cell viability, invasion, and migration ability decreased, and the number of apoptotic cells increased, will all indicators being statistically significant (P

Objective: This retrospective study aims to explore the risk factors for brain metastasis and the prognostic factors for overall survival (OS) in patients with limited-stage small-cell lung cancer (LS-SCLC) who have no brain metastases according to magnetic resonance imaging (MRI) and have not received prophylactic cranial irradiation (PCI) after first-line chemoradiotherapy. Methods: A total of 107 patients who were treated in the Fourth Hospital of Hebei Medical University from January 2013 to December 2017 were enrolled in this study. The patients were treated with etoposide/platinum chemotherapy and thoracic radiotherapy (TRT) with involved-field irradiation. The median dose of the radiotherapy was 60 ​Gy (50−64 ​Gy). The primary study endpoints include BMFS (brain-metastasis-free survival) and OS (overall survival). The Kaplan-Meier method was applied to estimate survival, with a log-rank test used to ascertain statistical significance. The multivariate Cox proportional hazards model was used to determine the prognostic factors for survival. Results: The median follow-up of all patients was 18.8 months (range: 7.9–65.1 months) and the median follow-up of surviving patients was 26.7 months (range: 18.8–65.1 months). The median OS of the whole cohort was 20.1 months, and the 1-, 2- and 3-year OS rates were 84.9%, 44.9%, and 25.9%, respectively. The 1-, 2-, and 3-year BMFS rates were 69.0%, 49.9%, and 40.7%, respectively. 50 patients (46.7%) developed brain metastases during the follow-up period, and the median time from the start to brain metastasis was 10.7 months (range: 4.8–31.1 months). As shown by multivariate analysis, independent prognostic factors of OS included cycles of chemotherapy (P ​= ​0.019), the response to initial treatment (P ​= ​0.011), and the start time of TRT (P ​= ​0.044). The independent prognostic factors of BMFS included the clinical stage (P ​= ​0.008), the response to initial treatment (P ​= ​0.024), and the start time of TRT (P ​= ​0.028). Conclusions: For patients with LS-SCLC who have not received PCI, favorable factors for lower brain metastasis and higher survival include early clinical stage, CR to initial chemoradiotherapy, early TRT, and adequate cycles of chemotherapy. PCI is still recommended as the standard modality since the incidence of brain metastases was high (46.7%).

Objective: Angiogenesis plays an important role in the growth and metastasis of non-small cell lung cancer (NSCLC). Bevacizumab is a humanized monoclonal antibody that mainly acts on vascular endothelial growth factor A (VEGFA) . Kinase insert domain receptor (KDR) is the most important target of VEGFA . The aim of present study was to investigate the influence of KDR genetic variation on the efficacy and safety of patients with advanced NSCLC receiving first-line bevacizumab plus chemotherapy regimen. Methods: A total of 169 patients with advanced NSCLC who received bevacizumab combined with chemotherapy were recruited in this study. Clinical outcome of the regimens was evaluated in the hospital. Peripheral blood and biopsy tissue specimens of patients were collected for the genotyping of KDR genetic variation and KDR mRNA expression, respectively. The association between KDR genotype status and other variables were analyzed. Univariate analysis of genotype status and prognosis was implemented using the Kaplan-Meier survival analysis method. Multivariate Cox regression analysis was performed to adjust the confounding factors. Results: Of the polymorphisms analyzed, only V297 L was of clinical significance. The prevalence of V297 L among the study population were as follows: CC genotype 123 cases (72.8%), CT genotype 41 cases (24.3%), TT genotype 5 cases (2.9%). The minimum allele frequency is 0.15. The distribution frequencies of the 3 genotypes corresponded with Hardy-Weinberg equilibrium ( P = 0.489). Patients with TT and CT genotypes were merged in the subsequent comparison of clinical outcomes. The analysis of efficacy exhibited that the objective response rates (ORR) of patients with CC genotype and CT/TT genotypes were 52.8% and 47.8% ( P = 0.561), respectively. Prognosis indicated that the median progression free survival (PFS) of patients with CC genotype and CT/TT genotype were 8.9 and 5.5 months, respectively ( P = 0.006). The median OS of the 2 genotypes were 20.0 and 14.9 months, respectively ( P = 0.021). Adjusted in multivariate Cox regression analysis of PFS, CT/TT genotypes were an independent factor for PFS [hazard ratio (HR) = 1.59, P = 0.011). Safety profile according to genotype status of V297 L failed to find significant difference. Interestingly, the expression of KDR mRNA of patients with CT/TT genotype was significantly higher than that of patients with CC genotype in the 58 cancer tissue specimens ( P < 0.001). Conclusion: The clinical comes of patients with advanced NSCLC receiving first-line bevacizumab plus chemotherapy regimens might be impacted by polymorphism V297 L through mediating the mRNA expression of KDR .