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Purpose@#We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations. @*Materials and Methods@#This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint. @*Results@#The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment. @*Conclusion@#EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.
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Background and purpose:Neuropilin-1 (NRP1), a vascular endothelial growth factor (VEGF) receptor, plays an important role in tumor angiogenesis and tumor cell migration. The purpose of this study was to de-termine the correlation between NRP1 expression and sensitivity to ifrst-line platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC), and between NRP1 expression and survival.Methods:NRP1 ex-pression in tumor tissues of 104 advanced NSCLC patients treated with ifrst-line platinum-based regimen was detected by immunohistochemisty.A chi-square test and logistic regression model were used to analyze the relationship between NRP1 expression and the chemotherapy response rate. Kaplan-Meier and Cox proportional hazard regression models were used to analyze the effect of NRP1 expression on patient survival.Results:Among the 104 patients, 56 (53.8%) had high expression of NRP1. High expression of NRP1 was not related to age, gender, histological type, degree of differentiation, performance status, and chemotherapy regimen. The chemotherapy response rate was significantly higher in patients with low NRP1 expression than in patients with high expression (43.8% vs23.2%,P=0.026). The low NRP1 expression was signiifcantly associated with longer progression-free survival (4.6 monthsvs3.0 months, P=0.001 for log-rank test,χ2=11.273) and overall survival (11.5 monthsvs9.2 months,P=0.000 for log-rank test,χ2=14.392) as compared with high NRP1 expression. Multivariate analysis showed that high expression of NRP1 was an independent predictor for the chemotherapy response rate and overall survival in patients with advanced NSCLC.Conclusion:NRP1 expression is associated with response rate and survival in advanced NSCLC patients treated with ifrst-line plati-num-based chemotherapy. NRP1 expression may be a potential biomarker for predicting chemosensitivity and prognosis in patients with advanced NSCLC.
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<p><b>BACKGROUND</b>To investigate whether high-dose toremifene can enhance the efficacy of chemotherapy in non small cell lung cancer.</p><p><b>METHODS</b>Untreated stage IIIB/IV non-small cell lung cancer patients were randomly devided into group A (high-dose toremifene combined with the platinum-based chemotherapy) or group B (the same platinum-based chemotherapy alone).</p><p><b>RESULTS</b>A total of 30 eligible patients had been recruited. Hemotologic and nonhemotologic toxicities were similar with no statistic difference. The median survival for group A was 8 months, 95% CI (6.63-9.37) versus 7.5 months, 95% CI (4.75-10.25) for group B ( P =0.9). One year-survival rate was 31% for group A versus 28% for group B ( P =0.87). The response rate was 25% for group A versus 21% for group B ( P =0.99).</p><p><b>CONCLUSIONS</b>The results suggest that high-dose toremifene does not enhance the efficacy of platinum-based chemotherapy for IIIB/IV non-small cell lung cancer but toxicities are well tolerated.</p>