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.

The relationship between epidermal growth factor receptor (EGFR) mutation status and EGFR-tyrosine kinase inhibitors (TKI) efficacy in non-small cell lung cancer (NSCLC) patients has been well established. However, there is no available standard to define the optimal testing method and specimen type required for the detection of EGFR mutations. In this study, we compare results of ADx-amplification refractory mutation system (ARMS) and direct sequencing for the detection of EGFR mutation and prediction of EGFR-TKI efficacy for surgery and biopsy tumor tissues in 158 NSCLC patients. For 71 surgery samples, there were 13 and 17 positive samples detected by direct sequencing and ARMS, respectively. For 87 biopsy samples, direct sequencing and ADx-ARMS found 15 and 32 positive samples, respectively. For surgery samples, sensitivity of direct sequencing and ARMS was 72.2% (13/18) and 94.4% (17/18), respectively. For the biopsy samples, sensitivity of direct sequencing and ARMS was 44.1% (15/34) and 94.1% (32/34), respectively. For the biopsy and surgery samples, the ORRs for EGFR positive and negative patients detected by direct sequencing were 46.1 versus 16.7 and 66.7 versus 1.1%, respectively. For ADx-ARMS, the ORR for EGFR positive patients was significantly higher than for negative patients (55.6 vs. 5.6%). The median progression-free survival time of patients with EGFR wild type detected by direct sequencing (4.2 months) was significantly longer than that of patients with wild type detected by ARMS (1.7 months). ARMS has a higher sensitivity and specificity than direct sequencing for EGFR detection of mutation in both surgical and biopsy samples, and the results from ARMS are more consistent with the efficacy of EGFR-TKIs treatment.

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 firstline treatment; and sum of treatment lines (<2, ≥2). Student's t test or chi-squared test was used to analyze the associations between AAPR and clinical characteristics. Kaplan-Meier survival analysis and Cox's proportional hazards regression model were used to assess the prognostic value of AAPR for OS. Results: The average patient age was 60.51±8.73 years, and 87.95% were men. A non-linear relationship between AAPR and OS was detected, with an inflection point of 0.35. The hazard ratios (HRs) of the left (AAPR <0.35) and right sides (AAPR ≥0.35) of inflection point were 0.04 (95% CI=0.00-0.70, p=0.0268) and 0.52 (95% CI=0.16-1.64, p=0.2659), respectively. Kaplan-Meier analysis showed a median OS of 9.73 months (95% CI=8.6-12.33) for AAPR <0.35 and 13.7 months (95% CI=11.43-16.37) for AAPR ≥0.35 (log-rank p<0.0001). The Cox proportional hazards model showed that AAPR <0.35 increased the risk of death after adjusting for potential confounders (HR=1.65, 95% CI=1.11-2.46). In subgroup analysis, the trends of HRs were increased across all subgroups with AAPR <0.35 after stratification. Conclusion: Pretreatment AAPR might be served as an independent prognostic indicator in ED-SCLC patients. Our findings should be further validated in large-scale and prospective clinical trials.

EML4-ALK fusion genes have been recognized as novel "driver mutations" in a small subset of non-small cell lung cancers (NSCLC). The frequency of EML4-ALK fusions in NSCLC patients who have clinical characteristics related to EGFR mutation remains unknown. We screened 102 Chinese patients with NSCLC based on one or more of the following characteristics: female, no or light smoking history, and adenocarcinoma histology. EML4-ALK fusion genes were identified by RT-PCR, whereas EGFR (Exons 18-21) and KRAS (Exons 1 and 2) mutations were detected by DNA sequencing. Eight specimens (8%) were positive for EML4-ALK fusions, with seven being Variant 1 and one Variant 2. There were 44 (43%) and 17 (16%) patients harboring EGFR and KRAS mutations, respectively. Thirty-one (31%) cases were wild type for EML4-ALK, EGFR, and KRAS mutations. Of the eight patients with EML4-ALK, none had an EGFR mutation, whereas a KRAS mutation was detected in one patient. Histologically, five of the EML4-ALK positive tumors were adenocarcinoma and two were mixed adenosquamous carcinoma; only one was a squamous carcinoma. Our data support the conclusion that the EML4-ALK fusion gene defines a new molecular subset of NSCLC with distinct pathologic features.

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 < 0.34, n = 266), medium (AAPR = 0.34‐0.47, n = 259), and high (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 <.05). The median OS of low, medium, and high AAPR was 9.3, 11.8, and 16.9 months, respectively (P value <.0001). No optimal cutoff value of AAPR for prognosing OS was identified by smooth curve fitting. The HR and the 95% confidence intervals of the left and right sides of the inflection point 0.6 as cutoff value were 0.28 (95%CI = 0.14‐0.57) and 0.77 (95%CI = 0.34‐1.73), respectively (P value = .127). By subgroup analysis, similar results were consistently observed across nearly all the subgroups. Conclusion Our study implied that pretreatment AAPR can be used as an independent prognostic factor in patients with advanced NSCLC. This ratio should be applied for risk stratification and clinical decision‐making in those patients.

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ObjectiveThis 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).MethodsRetrospective 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.ResultsAmong 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.ConclusionEGFR-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.

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 <60 years. The percentages of GPS scores of 0, 1, and 2 were 36.44%, 36.03%, and 27.53%, respectively. The median OS of the GPS 0, 1, and 2 groups were 23.27, 14.37, and 10.27 months, respectively (log-rank P <0.0001). A higher GPS was independently associated with an increased risk of death (P for trend = 0.0004) after full adjustment for potential confounders. The risk of death increased by 77% in the GPS 1 group (hazard ratio [HR]=1.77, 95% confidence interval [CI]=1.22-2.57, P=0.0027) and 109% in the GPS 2 group (HR=2.09, 95%CI=1.36-3.22, P=0.0008) compared with the GPS 0 group after adjustment. We did not find significant heterogeneity among the analyzed subgroups apart from sex (P interaction=0.017). Conclusion: High pretreatment GPS is independently associated with worse OS in patients with advanced NSCLC. GPS should be considered in patient counseling and decision-making and needs to be further validated by large-cohort and prospective studies.