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PURPOSE The CHOICE-01 study investigated the efficacy and safety of toripalimab in combination with chemotherapy as a first-line treatment for advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS Patients (N = 465) with treatment-naive, advanced NSCLC without EGFR/ALK mutations were randomly assigned 2:1 to receive toripalimab 240 mg (n = 309) or placebo (n = 156) once every 3 weeks in combination with chemotherapy for 4-6 cycles, followed by the maintenance of toripalimab or placebo once every 3 weeks plus standard care. Stratification factors included programmed death ligand-1 expression status, histology, and smoking status. The primary end point was progression-free survival (PFS) by investigator per RECIST v1.1. Secondary end points included overall survival and safety. RESULTS At the final PFS analysis, PFS was significantly longer in the toripalimab arm than in the placebo arm (median PFS, 8.4 v 5.6 months, hazard ratio = 0.49; 95% CI, 0.39 to 0.61; two-sided P < .0001). At the interim OS analysis, the toripalimab arm had a significantly longer OS than the placebo arm (median OS not reached v 17.1 months, hazard ratio = 0.69; 95% CI, 0.53 to 0.92; two-sided P = .0099). The incidence of grade ≥ 3 adverse events was similar between the two arms. Treatment effects were similar regardless of programmed death ligand-1 status. Genomic analysis using whole-exome sequencing from 394 available tumor samples revealed that patients with high tumor mutational burden were associated with significantly better PFS in the toripalimab arm (median PFS 13.1 v 5.5 months, interaction P = .026). Notably, patients with mutations in the focal adhesion-PI3K-Akt signaling pathway achieved significantly better PFS and OS in the toripalimab arm (interaction P values ≤ .001). CONCLUSION Toripalimab plus chemotherapy significantly improves PFS and OS in patients with treatment-naive advanced NSCLC while having a manageable safety profile. Subgroup analysis showed the OS benefit was mainly driven by the nonsquamous subpopulation.

Background: The purpose of this study was to investigate whether pretreatment anemia was an independent risk factor for survival in patients with advanced non-small cell lung cancer (NSCLC) after adjusting for other covariates. Methods: We used propensity score matching (PSM) to minimize the influence of confounding factors and used χ2 (categorical variables), Student's t-test (normal distribution), or Mann-Whitney U test (skewed distribution) to analyze the differences among the Hb groups. Cox regression and Kaplan-Meier analyses were used to assess the association between anemia and survival. P values < 0.05 (two-sided) were considered statistically significant. Results: The average age of the 758 selected participants was 58.2±11 years, and 210 patients (27.7%) had anemia. In the multivariate analysis, anemia was associated with a poor prognosis in the unmatched cohort (Hazards ratio (HR)=1.3, 95% (confidence interval (CI): 1.1-1.6; p= 0.008), and the matched cohort (HR=1.7, 95% CI: 1.3-2.3; p

Background: Findings from previous studies regarding the association between the Glasgow Prognostic Score (GPS) and overall survival (OS) of patients with advanced non-small cell lung cancer (NSCLC) were limited. This study aimed to investigate the prognostic value of GPS in patients with advanced NSCLC after adjusting for potential confounding factors. Methods: A retrospective cohort study was conducted in 494 patients with advanced NSCLC between 2009 and 2019. Clinicopathological characteristics (including GPS) were analyzed to determine predictors of OS using univariate and multivariate Cox proportional hazards models. Survival curves were estimated using the Kaplan-Meier method. Results: Of the enrolled patients with advanced NSCLC, 66.46% were men and 53.85% were aged

Objectives To investigate the relation between AAPR and OS in patients with advanced non‐small cell lung cancer (NSCLC). Methods A retrospective cohort study was conducted with 808 patients with advanced NSCLC who were treated in Guangxi Medical University Affiliated Tumor Hospital in China from 5 March 2009 to 31 August 2018. The target‐independent and dependent variables were AAPR measured in patients before anticancer treatment and overall survival (OS), respectively. Covariates involved in this study included age, gender, ECOG status, smoking history, clinical stages, pathological type, driver mutation (EGFR or ALK), metastasis or not (bone, lung, liver, brain, malignant plural effusion, and other organs), number of organ metastasis(≤3, >3), first‐line regiment and number of treatment lines (≤3, >3). Results The mean age of the selected patients was 58.3 ± 10.9 years and 68.6% were male. We divided patients according to their AAPR into low (AAPR 0.47, n = 283) tertile groups. Medium and high AAPR were associated with a decreased risk of death after fully adjusted Cox proportional hazard model(s) with hazards ratio (HR) 0.77 (95%CI = 0.58‐1.03) and HR 0.59 (95%CI = 0.45‐0.78), respectively (P for trend, Using a retrospective cohort study with a large number of patients, this study investigates the relationships between albumin‐to‐alkaline phosphatase ratio as a prognostic factor for patients with advanced non‐small cell lung cancer.

Purpose Evidence regarding the relationship between albumin-to-alkaline phosphatase ratio (AAPR) and overall survival (OS) in extensive-disease small-cell lung cancer (ED-SCLC) patients is limited. This study aimed to investigate whether AAPR was independently related to OS in ED-SCLC patients after adjusting for potential covariates. Patients and Methods This was a retrospective cohort study of 224 patients with ED-SCLC. The target independent and dependent variables were pretreatment AAPR and OS, respectively. Covariates included age; sex; Eastern Cooperative Oncology performance status score; smoking history; existence of metastasis to organs such as the bone, lung, liver, brain, malignant plural effusion and others; sum of organ metastasis (≤3, >3), evaluation of first-line treatment; and sum of treatment lines (

Chengliang Yuan, Huiqin Jiang, Wei Jiang, Huilin Wang, Cuiyun Su, Shaozhang Zhou Department of Respiratory Oncology, Guangxi Medical University Affiliated Tumor Hospital, Nanning City, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of ChinaCorrespondence: Shaozhang Zhou; Cuiyun SuDepartment of Respiratory Oncology, Guangxi Medical University Affiliated Tumor Hospital, No. 71 Heti Road, Nanning City, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of ChinaTel +86-0771-5320761; +86-0771-5334955Fax +86-0771-5300613Email zhoushaozhang@gxmu.edu.cn; 503893236@qq.comPurpose: The purpose of this study is to compare the different EGFR mutation status in patients with metastatic non-small cell lung cancer (NSCLC) after first-line EGFR-TKIs therapy and analyze its relationship with efficacy and prognosis.Patients and Methods: This study retrospectively analyzed the data of patients with metastatic NSCLC harboring EGFR mutation in the Affiliated Tumor Hospital of Guangxi Medical University from June 2016 to December 2020. Samples were collected before treatment and at the time of disease progression after first-line EGFR-TKIs therapy. Amplification refractory mutation system (ARMS) PCR and next-generation sequencing (NGS) were used to detect EGFR mutation. ORR, DCR, and PFS of different EGFR mutation groups were compared.Results: The EGFR mutation rate of re-biopsy was 60.23%. The inconsistency rate of EGFR mutations in the same and different simple types was 72.22% (26/36) and 92.31% (48/52), respectively. Alterations in terms of EGFR mutations were divided into four groups: Group A: EGFR-sensitive mutation negative and T790M negative (39.77%); Group B: EGFR-sensitive mutation positive and T790M negative (18.19%); Group C: EGFR-sensitive mutation negative and T790M positive (36.36%); Group D: EGFR-sensitive mutation positive and T790M positive (5.68%). The differences between the four groups in ORR and DCR were not statistically significant (P> 0.05). The median PFS of all patients was 10.65 months. PFS of Group A, B, C, and D was 12.26, 7.96, 10.55, and 13.81 months, respectively, with statistical significance (Log rank P = 0.014).Conclusion: EGFR mutation status in metastatic NSCLC patients receiving the first- and second-generation TKIs after disease progression show diversity. Monitoring the EGFR mutation changes is of great importance for subsequent clinical decision-making and exploring the underlying mechanisms of acquired resistance.Keywords: non-small cell lung cancer, EGFR-TKIs, re-biopsy, EGFR gene mutation status

BackgroundThe purpose of this study was set to investigate the prognostic role of plasmatic levels of heat shock protein 90 alpha (HSP90α) at diagnosis in advanced lung cancer patients treated with Programmed cell death protein 1 (PD-1)/Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus chemotherapy.MethodsA total of 137 advanced lung cancer patients treated with PD-1/PD-L1 inhibitors plus chemotherapy admitted to the Guangxi Medical University Cancer Hospital were enrolled in this study. Smooth curve fitting was conducted to address the nonlinearity of HSP90α and progression-free survival (PFS) and overall survival (OS). We calculated the inflection point using a recursive algorithm. Kaplan–Meier survival analysis and Cox proportional hazards regression model were used to assess the prognostic value of HSP90α for PFS and OS. Subgroup analysis was performed to evaluate the relationship between high HSP90α and disease progression and death risk.ResultsThe average age of patients was 58.6 ± 9.8 years, and 73.7% of them were men. We divided patients according to their plasmatic levels of HSP90α into low (HSP90α ConclusionPlasmatic levels of HSP90α at diagnosis can be considered a potential independent prognostic marker of advanced lung cancer patients treated with PD-1/PD-L1 inhibitors plus chemotherapy. A further large-scale prospective validation study is needed to determine whether these results are widely applicable.

Objective This study analyzed the relationship between the clinicopathological features and epidermal growth factor receptor (EGFR) mutation status of squamous cell lung cancer (SqCLC) patients. Mutation status was analyzed by comparing the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and next-generation sequencing (NGS). We also assessed the efficacies of EGFR tyrosine kinase inhibitors (TKIs). Methods Retrospective analysis was performed for 292 SqCLC patients treated at the Guangxi Medical University Affiliated Tumor Hospital from December 2013 to December 2018. The EGFR mutations in tumor tissues were identified by ARMS-PCR and NGS. The affiliation between EGFR mutation and clinicopathological features was analyzed. Efficacies of EGFR-TKIs and survival were evaluated using the benchmarks of response evaluation criteria in solid tumors 1.1 (RECIST 1.1) and the Kaplan-Meier method, respectively. Results Among the 292 SqCLC patients, 24 (8.2%) were identified to have an EGFR-sensitizing mutation. Both ARMS-PCR and NGS were equally effective in detecting EGFR mutations. Females and non-smokers had higher EGFR mutation rates than males and smokers (22.1% vs. 5.1%, P = 0.007 and 16.7% vs. 4.5%, P = 0.001, respectively). EGFR mutation was unrelated to the degree of differentiation, clinical stage, specimen type and level of serum carcino-embryonic antigen (CEA) and squamous cell carcinoma antigen (SCC) (P > 0.05). In the 14 EGFR mutant cases treated with EGFR-TKIs, the objective response rate (ORR) and disease control rate (DCR) were 28.6% and 78.6%, respectively. Median progression-free survival (mPFS) and overall survival (mOS) were 4.9 and 10.75 months, respectively, with fine tolerance and mild side-effects. Conclusion EGFR-sensitizing mutations are rare in SqCLC patients with females and non-smokers having a higher risk of harboring them. There was no difference in the detection rates of EGFR for both the ARMS-PCR and NGS methods. EGFR-TKIs showed modest efficacies and low toxicity profiles in EGFR mutant cases.

Feiwen Liu,1 Shaozhang Zhou,1,2 Liping Tan,2 Huiqin Jiang,1 Yucong Huang1 1Oncology Medical College, Guangxi Medical University, Nanning City 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Respiratory Oncology, Guangxi Medical University Affiliated Tumor Hospital, Nanning City 530021, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaCorrespondence: Shaozhang Zhou; Liping TanDepartment of Respiratory Oncology, Guangxi Medical University Affiliated Tumor Hospital, No. 71 Heti Road, Nanning City 530021, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaTel +86-13977183708; +86-18776404799Fax +86-771-5300613Email zhoushaozhang@gxmu.edu.cn; 988tan@163.comPurpose: Neutrophil-to-lymphocyte ratio (NLR) has been suggested as an independent risk factor for progression-free survival (PFS) and overall survival (OS) in small cell lung cancer (SCLC). However, it is still unknown whether there is a linear relationship between the NLR and the risk of death in SCLC. The objective of this study is to provide further results.Patients and Methods: A retrospective cohort study was performed among a total of 251 participants with SCLC. Smooth curve fitting and piecewise Cox regression model were used to determine the linear relationship between NLR and mortality risk. A multivariable Cox regression model was used to estimate the effects of NLR on OS. Interaction and stratified analyses were conducted according to covariates.Results: The analysis indicated no significant nonlinear relationship or threshold effect between NLR and hazard of death. Multivariate analysis revealed that every unit increase in NLR was associated with a 10% increase in mortality risk. High NLR (> 3.5) at baseline was associated with poor OS (hazard ratio [HR]=1.97, P=0.009). The difference in median OS duration between the high and low NLR groups was statistically significant (9.1 months vs 14.6 months, P=0.0067). Furthermore, interaction analysis identified the chemotherapy regimen to play an interactive role in the association between NLR and hazard of death.Conclusion: NLR was identified as an independent risk factor for OS in SCLC and the linear correlation was observed between them. Administration of etoposide plus cisplatin (EP) regimen in patients with low NLR resulted in better long-term outcome than that of etoposide plus carboplatin (EC) regimen, while administration of the EC regimen conferred longer OS than that of the EP regimen in patients with high NLR.Keywords: neutrophil-to-lymphocyte ratio, NLR, overall survival, small cell lung cancer, SCLC, etoposide plus carboplatin/cisplatin, mortality risk

Objective To evaluate the prognostic accuracy of d-dimer levels for advanced non-small-cell lung cancer (NSCLC). Methods This retrospective cohort study included 651 patients initially diagnosed with advanced NSCLC. Patients with d-dimer levels ≥0.5 mg/L were included in the high d-dimer group, whereas patients with lower levels were included in the normal group. Cumulative survival was estimated using Kaplan–Meier curves and compared using the log-rank test. Multivariate analyses were performed using the Cox proportional hazards model. Results The median plasma d-dimer level in the study cohort was 0.61 ± 0.49 mg/L. d-dimer levels were elevated in 60.98% of patients, and 80.1% of such patients had adenocarcinoma. Univariate and multivariate analyses identified d-dimer content as an independent factor for the prognosis of NSCLC (hazard ratio [HR] = 1.54, 95% confidence interval [CI] = 1.19–1.98). Kaplan–Meier analysis revealed that high plasma d-dimer levels were associated with shorter overall survival (HR = 1.48, 95% CI = 1.19–1.84). In addition, the receipt of 2 lines. Conclusion The present results imply that pretreatment plasma d-dimer levels could represent a prognostic factor for advanced NSCLC.

Previous studies have suggested that a variety of tumor driver genetic alterations affected the treatment efficacy of chemotherapy and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). The present study aimed to investigate the association between the tumor genetic alteration landscape and the treatment outcome of first-line chemotherapy and EGFR-TKIs in advanced NSCLC. A total of 94 patients with advanced NSCLC were recruited. All patients received first-line chemotherapy and/or EGFR-TKIs (either first- or second-generation EGFR-TKI, or third-generation EGFR-TKI) alone or sequentially. Prior to chemotherapy and/or EGFR-TKI treatment, plasma, effusion and/or tumor tissues from the included patients were subjected to next-generation sequencing, targeting 59 genes. The results indicated that the positive genetic alteration status prior to first-line chemotherapy was associated with prolonged progression-free survival (PFS) time compared with the negative status [9.1 vs. 4.0 months; hazard ratio (HR)=6.68; 95% CI, 2.25-19.82; P=0.001). Furthermore, patients with EGFR activating mutation harboring concomitant alterations exhibited a shorter PFS (11.1 vs. 7.4 months; HR=2.14; 95% CI, 1.03-4.44; P=0.04) and overall survival (OS) time [not reached (NR) vs. 32.8 months; HR=4.30; 95% CI, 1.41-13.16; P=0.01] than those without concomitant alterations, with first- and second-generation EGFR-TKI treatment. Similarly, patients with T79M mutation harboring concomitant alterations exhibited a shorter PFS (15.6 vs. 3.6 months; HR=9.48; 95% CI, 2.29-39.28; P=0.002) and OS time (NR vs. 32.8 months; HR=4.85; 95% CI, 1.16-20.29; P=0.03) with osimertinib treatment. Taken together, the results demonstrated that positive genetic alteration status predicted greater efficacy of first-line chemotherapy, while concomitant genetic alterations were associated with poor treatment outcome for first- or second-generation EGFR-TKI and third-generation EGFR-TKI treatment.

Overexpression of insulin growth factor 1 receptor (IGF-1R) and its ligand, insulin growth factor 1 (IGF-1), is related to treatment resistance and worse prognosis in many types of tumors. We reported recently that IGF-1R activation by IGF induces resistance to alectinib and stimulates the production of vascular endothelial growth factor, which indicates that IGF induces alectinib resistance and angiogenesis. This study aimed to determine the effect of bigeminal inhibition of anaplastic lymphoma kinase (ALK) and angiogenesis on human insulin growth factor 1 receptor (hIGF-1)-triggered drug resistance in echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK)-positive lung cancer. Human lung adenocarcinoma H3122 and H2228 cells were exposed to a combination of insulin growth factor 1 receptor (IGF-1), alectinib, or apatinib. The effects of the combination therapy were examined using cell the Cell Counting Kit-8 assay, the colony-forming assay, the scratch test, and flow cytometry analysis, and the molecular mechanism was assessed by western blot. At nontoxic concentrations, apatinib restored alectinib sensitivity by increasing drug-induced apoptosis and inhibiting viability, migration, and invasion in IGF-triggered drug resistant cells. Moreover, we found that apatinib restored sensitivity to alectinib mainly through suppression of the ALK downstream signaling pathway and antiangiogenesis signaling. Taken together, our results indicate that simultaneous inhibition of ALK and vascular endothelial growth factor R2 by the combination of alectinib with apatinib may be useful for controlling progression of EML4-ALK fusion gene lung cancer by reversing ALK-TKI resistance and inhibiting angiogenesis.

e21077 Background: Previous studies indicated primary resistance to EGFR-TKIs might occur in EGFR co-mutation with other oncogenic alterations. However, the optimal therapeutic regimen for advanced NSCLC with EGFR co-mutation was still unknown. This respective observation study aimed to assess the efficacy and safety of the combination therapy with EGFR-TKI and chemotherapy in this sub-population. Methods: In this retrospectively study, from March 2017 to November 2019 advanced NSCLC patients with EGFR mutation detected using next-generation sequencing targeting 59 genes were screened for eligibility. We included patients of EGFR co-mutation with other oncogenic alterations receiving EGFR-TKI monotherapy or TKI plus chemotherapy as first-line therapy. The primary outcome was objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Disease control rate (DCR) and safety profile were considered to be the secondary endpoints. Results: Total 48 patients were enrolled. Among patients with concomitant mutation, the combination of chemotherapy with TKI was found to prolong mPFS (12.5 vs 7.3 months; HR, 0.38; 95%CI: 0.17-0.81; P = 0.012) compared with TKI monotherapy, with a trend of longer mOS (27.0 vs 22.4 months; HR, 0.40; 95%CI: 0.15-1.05; P = 0.062) and higher ORR (68.4% vs 44.8%, P = 0.113). The DCR were 100% in combination group and 93.1% in monotherapy group (P = 0.99). A proportion of 13.8% patients reported grade≥3 treatment-related adverse events in monotherapy group and 36.8% in combination group. Conclusions: EGFR co-mutation with other oncogenic alterations associated with poor treatment outcome with EGFR-TKI monotherapy. The combination of EGFR-TKI and chemotherapy was effective in this sub-population and side-effects were tolerable. The outcomes of this study should be confirmed by prospective clinical trials in future.

Objective To investigate the prognostic value of pretreatment haemoglobin-to-red cell distribution width radio (HRR) in predicting overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC). Methods This retrospective study analysed patients with advanced NSCLC. Kaplan–Meier survival analysis and Cox proportional hazards regression analysis were conducted to evaluate the predictive value of HRR for OS. A propensity matching analysis was used to reduce the impact of other confounding factors on the results. Results A total of 448 patients were enrolled in the study. The median HRR was 0.984, which was used as the cut-off value. Regardless of matching or not, a lower HRR was correlated with an unfavourable risk of death. After propensity matching, univariate and multivariate analysis showed that HRR was an independent factor for the prognosis of NSCLC (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.17, 2.04; HR 1.57, 95% CI, 1.17, 2.10; respectively). Kaplan–Meier analysis showed that low HRR was associated with shortened OS. The relationship between HRR and the risk of death was consistent across all patient subgroups after stratification by subgroup analysis. Conclusions These findings showed that a lower pretreatment HRR could be a potentially valuable prognostic factor in patients with advanced NSCLC.