First-line pemetrexed-platinum doublet chemotherapy with or without bevacizumab in non-squamous non-small cell lung cancer: A real-world propensity score-matched study in China

Objective: To evaluate the efficacy and safety profile of first-line bevacizumab(Bev)-containing pemetrexedplatinum chemotherapy in a real-world Chinese cohort with advanced non-squamous non-small cell lung cancer(NS-NSCLC).Methods: A total of 415 eligible patients with NS-NSCLC who received first-line pemetrexed-platinum chemotherapy at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between February 2010 and September 2017 were reviewed retrospectively: 309 Bev(-) and 106 Bev(+) cases. Bev was administered at 7.5 mg/kg every 3 weeks in the Bev(+) group. To reduce the risk of a selection bias, a propensity score-matching(PSM) was conducted and 105 pairs of Bev(-) and Bev(+) cases were identified.Results: The median duration of follow-up was 15.8 months. The median progression-free survival(PFS) was prolonged significantly in the Bev(+) group than in the Bev(-) group in overall(9.8 vs. 7.8 months, P=0.006) and PSM pairs(9.8 vs. 6.6 months, P<0.001). Moreover, patients receiving maintenance therapy with pemetrexed plus Bev had longer PFS than those interrupted after induction chemotherapy, or those receiving mono-maintenance with pemetrexed(12.3 vs. 4.8 vs. 8.6 months;P<0.001). Multivariate analyses revealed Bev to be one of the favorable prognostic factors for PFS, along with the predictor of maintenance therapy.Conclusions: First-line induction and maintenance therapy with Bev(7.5 mg/kg every 3 weeks) combined with pemetrexed-platinum chemotherapy was efficacious and superior to non-Bev chemotherapy in Chinese patients with advanced NS-NSCLC.

Equivalent efficacy study of QL1101 and bevacizumab on untreated advanced non-squamous non-small cell lung cancer patients: a phase 3 randomized, double-blind clinical trial

Objective:This phase 3 study aimed to test equivalence in efficacy and safety for QL1101,a bevacizumab analogue in Chinese patients with untreated locally advanced non-squamous non-small cell lung cancer(NSCLC).Methods:Eligible patients were randomly assigned 1:1 to receive carboplatin and paclitaxel in combination with either QL1101 or bevacizumab,15 mg/kg every 3-week for 6 cycles.This was followed by maintenance treatment with single agent QL1101 every 3-week.The primary end-point was objective response rate(ORR),with secondary end-points being progression-free survival(PFS),overall survival(OS),disease control rate(DCR),and adverse events(AEs).Results:Of 675 patients,535 eligible patients were randomized to the QL1101 group(n=269)and bevacizumab group(n=266).ORRs were 52.8%and 56.8%,respectively,for the QL1101 and bevacizumab groups,with an ORR hazard ratio 0.93(95%confidence interval:0.8-0131.1).The PFS,OS,DCR,and AEs were comparable between the 2 groups,which remained the same after stratification according to epidermal growth factor receptor mutation or smoking history.Conclusions:QL1101 showed similar efficacy and safety profiles as compared to bevacizumab among Chinese patients with untreated locally advanced non-squamous NSCLC.

Predictive Factors of Severe Toxicities of Pemetrexed-Containing Chemotherapy in Patients with Non-Squamous Non-Small Cell Lung Cancer

Background: Pemetrexed (PEM) is an efficacious multi-targeted antifolate with acceptable toxicities for non-squamous non-small cell lung cancer (non-Sq NSCLC). However, in the clinical setting, PEM has more severe adverse effects than those reported. The aim of this study was to identify the factors for the toxicities of PEM-containing chemotherapy in non-Sq NSCLC patients in the clinical setting. Patients and Methods: We retrospectively evaluated the factors related to PEM toxicities in chemotherapy-naive patients with non-Sq NSCLC from September 2009 to July 2013 at our hospital. Logistic regression model was used in the univariate and multivariate analyses. Results: In total, 104 patients were analyzed. Grades 3 to 5 hematologic toxicities were frequent and included neutropenia (42%), febrile neutropenia (7%), anemia (18%), thrombocytopenia (17%), and disseminated intravascular coagulation (2%). On multivariate analyses, the predictors were poor performance status (PS) [odds ratio (OR): 4.89, 95% confidence interval (CI): 1.22 - 19.4] and low body mass index (OR: 1.44, 95% CI: 1.05 - 1.98) for febrile neutropenia;concomitant chronic infectious disease (OR: 6.63, 95% CI: 1.59 - 27.5) and bevacizumab use (OR: 3.57, 95% CI: 1.36 - 9.32) for neutropenia;poor PS (OR: 3.02, 95% CI: 1.33 - 6.85) for thrombocytopenia;and low serum albumin level (OR: 0.22, 95% CI: 0.08 - 0.63) for non-hematologic toxicities. Conclusions: In addition to the previously reported predictors of PEM toxicities, the presence of concomitant chronic infectious disease was associated with hematologic toxicities. Patient groups who are not sufficiently evaluated in clinical trials should be carefully monitored for the development of more toxicities than expected.

Effect of Pemetrexed combined with cis-platinum chemotherapy on matrix metalloproteinase VEGF, NK cells and immune function in patients with non-squamous non-small cell lung cancer

Objective:To explore effect of Pemetrexed combined with cis-platinum chemotherapy on matrix metalloproteinase (MMPs), vascular esandothelial growth factor (VEGF), NK cells and immune function in patients with non-squamous non-small cell lung cancer.Method:A total of86 cases of non-squamous non-small cell lung cancer patients were divided into control group (n=44) and observation group (n=42), control group was given docetaxel combined cis-platinum chemotherapy, pemetrexed combined cis-platinum chemotherapy, was applied for observation group. Compared MMP-2, MMP-9, VEGF, NK cells and immune function level before and after treatment in both groups.Results: MMP-2, MMP-9, VEGF, NK cells, CD3+, CD4+, CD8+, CD4+/CD8+ level in both groups before treatment was no significant difference. After treatment, MMP-2, MMP-9, VEGF, CD8+level in both groups was significant lower than before treatment intra-group, and observation was lower than control group, there was significant difference. After treatment, NK cells, CD3+, CD4+, CD8+, CD4+/CD8+ level in both groups was increased dramatically than before treatment of intra-group, moreover, NK cells, CD3+, CD4+, CD8+, CD4+/CD8+level in observation group after treatment was obvious higher than in control group after treatment, there was significant difference.Conclusion:Pemetrexed combined with cis-platinum chemotherapy for non-squamous non-small cell lung cancer could effectively decrease serum MMPs, VEGF level and increase NK cell level, regulate immune function, with definite clinical significance.

Cost-effectiveness analysis of second-line chemotherapy strategies for patients with advanced non-squamous non-small cell lung cancer

Lung cancer is the most widespread type of cancer and the primary cause of cancer-related death in the world.In this study,we aimed to analyze the cost-effectiveness of second-line chemotherapy strategies based on gemcitabine,pemetrexed,and docetaxel for advanced non-squamous non-small cell lung cancer patients in China.A Markov model based on three states,progression-free survival,progressed survival and death,was constructed to simulate the progression of the disease in a 6-year horizon.Sensitivity analysis was performed to evaluate the robustness of the model.The primary outcome of the model was the incremental cost-effectiveness ratio at a willingness-to-pay threshold of 3×per capita GDP of China in 2018($29383).The baseline model results showed that the quality-adjusted life years over the course of the disease associated with second-line chemotherapy strategies were 0.233,0.417 and 0.272 for gemcitabine,pemetrexed and docetaxel,respectively,and the corresponding total costs were$5321.02,$12143.94,and$9479.42.Gemcitabine,pemetrexed and docetaxel resulted in the incremental cost-effectiveness ratios of$37081.09 and$106625.64 per quality-adjusted life year gained.The incremental cost-effectiveness ratio of pemetrexed and docetaxel compared with gemcitabine exceeded the willingness-to-pay threshold.One-way sensitivity analysis showed that the utility value of gemcitabine in the progressed survival state was the most influential parameter.

晚期非鳞状非小细胞肺癌患者直接非医疗经济负担及影响因素分析

目的系统分析无表皮生长因子/间变性淋巴瘤激酶(epidermal grouth factor receptor/anaplastic lymphoma kinase,EGFR/ALK)突变的晚期非鳞状非小细胞肺癌(non-small cell lung cancer,NSCLC)患者在疾病治疗过程中发生的直接非医疗费用,分析疾病所致直接非医疗经济负担及其影响因素,以期为制定降低非鳞癌患者疾病相关经济负担的有效措施提供决策建议与参考依据。方法采用方便抽样与整群抽样结合的方法,于2020年11月—2021年6月对上海市、江苏省、福建省、山东省和四川省12家医院的晚期非鳞状NSCLC患者进行一对一问卷调查,收集社会人口学信息和疾病信息,计算患病以来的直接非医疗费用,并利用广义线性回归模型分析其影响因素。结果本研究共纳入目标患者361名,患者自确诊以来的例均直接非医疗费用为13277.33元,其中,营养费用占比最高(30.3%),营养费用、就诊过程相关食宿费用的累积占比为84.6%。将直接非医疗费用及其5类组成部分分别作为因变量,与各变量纳入广义线性回归模型,结果显示:住院次数、平均住院天数对患者的总直接非医疗费用、住宿费用及伙食费用的影响具有统计学意义(P<0.05);病程对患者的总直接非医疗费用及营养费用的影响具有统计学意义(P<0.05);职业类型显著影响患者的总直接医疗费用、伙食及营养费用;独居情况显著影响患者的护工费用;住院次数和户籍显著影响患者的交通费用。结论晚期非鳞状NSCLC患者的直接非医疗负担不可忽视,建议:继续提升国家整体的肿瘤诊疗水平,持续强化县级龙头医院肿瘤综合防治能力,缩小城乡及省际诊疗水平差距;积极推进NSCLC的早诊早治与早期干预,提高患者生存率;通过健全多层次保障体系,提供多方经济补助;推动营养干预早期介入、提倡多样化护理形式等,借助多途径缓解晚期非鳞状NSCLC患者的直接非医疗负担。

Immunotherapy – new perspective in lung cancer

Lung carcinoma is associated with a high mortality worldwide,being the leading cause of cancer death.It is mainly classified into squamous non-small cell lung cancer(NSCLC),non-squamous NSCLC,and small cell lung cancer.However,such malignancy has been increasingly subdivided into histological and molecular subtypes to guide treatment.Therapies can be used in adjuvant and palliative settings.Regarding immunotherapy,it has been widely tested in both first or subsequent palliative lines.In this sense,drugs such as pembrolizumab,nivolumab,atezolizumab,ipilimumab,avelumab,and durvalumab have been assessed in large studies.Some of these trials have also studied these medicines in adjuvant and in maintenance therapy.In recent years,advances in immunotherapy have raised the hope that the unfavorable prognosis observed in several affected individuals can be changed.Immunotherapy has increased the overall survival in squamous NSCLC,non-squamous NSCLC,and small cell lung cancer.However,it has added to the oncology practice some side effects that are unusual in standard chemotherapy and require special clinical support.In order to show how immunotherapy is being applied in the treatment of lung carcinoma,we reviewed the main studies in adjuvant and palliative scenarios.What is the better scheme?What is the better combination?What is the better dose?When should we use immunotherapy?Does programmed cell death ligand 1 expression significantly interfere in immunotherapy efficiency?Some of these questions have already been answered,while others require more investigations.

Efficacy of ICIs on patients with oncogene-driven non-small cell lung cancer:a retrospective study

Aim:The objective of our study was to assess the efficacy of immune checkpoint inhibitors(ICIs)on patients with non-small-cell lung cancer(NSCLC)harboring oncogenic alterations.Methods:We retrospectively enrolled patients with advanced non-squamous NSCLC who were treated with anti-PD-1-based monotherapy or combined immunotherapy.Major characteristics including PD-L1 expression,treatment,and survival were analyzed.Results:In total,309 non-squamous NSCLC patients with a median age of 61 years(range 20-88 years)including 70.9%male were retrospectively enrolled.The molecular alterations involved epidermal growth factor receptor(EGFR)(n=81),V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS)(n=31),anaplastic lymphoma kinase(ALK)(n=1),human epidermal growth factor receptor 2(HER2)(n=12),V-raf murine sarcoma viral oncogene homolog(BRAF)(n=2),rearranged during transfection(n=4),and c-ros oncogene 1(ROS1)(n=3).In the EGFR subset,the ORR was 30.9%(n=81)and PFS was significantly shorter than WT group(median PFS:5.7 months vs.7.1 months;P=0.0061).In subgroup analyses,ICI combined therapy was significantly correlated with a longer PFS compared with ICI monotherapy(median PFS:7.7 months vs.4.7 months;P=0.0112).In KRAS patients,ORR was 51.6%(n=31).No significant difference was found in subgroup analyses.The ORR and PFS were 16.7%(n=12)and 28.6%(n=7),7.8 months and 9.0 months for HER2 and EGFR Exon20 insertion patients,respectively.Three ROS1 patients were enrolled with a PFS of 16.0,34.2,and 45.0 months individually,and one ALK patient with PFS of 4.4 months was identified.No response was found in two BRAF patients.Conclusion:ICI-based combination therapy can bring benefit to patients with EGFR-mutant NSCLC.ICI-based combination therapy could be considered for patients with ROS1 rearrangement,HER2 mutation and EGFR Exon20 insertion NSCLC.