Front-Line ICI-Based Combination Therapy Post-TKI Resistance May Improve Survival in NSCLC Patients With EGFR Mutation.

BACKGROUND: Data on the use of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation are limited. The current study aimed to assess the efficacy of ICIs in EGFR-mutant advanced NSCLC and explore the relevant influential factors. MATERIALS AND METHODS: Relevant clinical data of EGFR-mutant NSCLC patients who had received ICIs were collected from multiple hospitals. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), and relevant influential factors. RESULTS: A total of 122 advanced EGFR-mutant NSCLC patients were included in the final analysis. The total cohort had an objective response rate (ORR) of 32.0%, a median progression-free survival (mPFS) of 5.0 months, and a median overall survival (mOS) of 14.4 months. Among 96 patients with common EGFR mutations (19Del, 52 patients; L858R, 44 patients), those who were administered front-line ICI exhibited better survival benefits than those who received later-line ICI after disease progression on tyrosine kinase inhibitors (TKIs) treatment (mPFS: 7.2 months vs. 3.4 months, respectively, P < 0.0001; mOS: 15.1 months vs. 8.4 months, respectively, P <0.0001). Moreover, the efficacy of ICI-based combination therapy was better than that of ICI monotherapy (mPFS: 5.0 months vs. 2.2 months, respectively, P = 0.002; mOS: 14.4 months vs. 7.0 months, respectively, P = 0.001). Multivariate analysis showed that ICI-based combination therapy and front-line ICI administration after progression on EGFR-TKI were associated with significant improvements in both PFS and OS (P < 0.05). A high PD-L1 expression (tumor proportion score, TPS≥50%) and the EGFR L858R mutation were only significantly associated with a better PFS (P <0.05). A better Eastern Cooperative Oncology Group (ECOG) status was independently associated with a favorable OS (P <0.05). CONCLUSIONS: Taken together, combination immunotherapy in front-line was associated with improvement of survival in EGFR-mutant NSCLC patients post-TKI resistance. Further prospective studies with large sample sizes are required to identify the optimal combinatorial treatment strategy.

Prognostic value of lncRNA FEZF1 antisense RNA 1 over-expression in oncologic outcomes of patients with solid tumors.

BACKGROUND: FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1), as a novel lncRNA, was reported to be up-regulated in various cancers and involved in tumor progression. This study systematically assessed the prognostic value of FEZF1-AS1 in solid tumors. METHODS: Web of Science, PubMed, EMBASE, Chinese National Knowledge Infrastructure, and Wanfang databases were searched for eligible studies that evaluated the prognostic role of FEZF1-AS1 expression in cancer patients. Pooled hazard ratios (HRs) and combined odds ratios (ORs) with their 95% confidence intervals (CIs) were calculated. The meta-analysis was conducted using Stata/SE 14.1. RESULTS: Fifteen original studies involving 1378 patients were enrolled. Pooled results showed that increased expression of FEZF1-AS1 significantly correlated with shorter overall survival (OS) in cancer patients (HR 2.04, 95% CI 1.60-2.47), and also shorter disease-free survival (DFS) (HR 2.08, 95% CI 1.27-2.89). Additionally, the combined ORs indicated that increased FEZF1-AS1 expression was significantly associated with lymph node metastasis (OR 3.35, 95% CI 1.98-5.67), distant metastasis (OR 3.10, 95% CI 1.86-5.15), poor tumor differentiation (OR 2.90, 95% CI 1.45-5.80), high depth of tumor invasion (OR 2.72, 95% CI 1.36-5.43), and advanced clinical stage (OR 2.76, 95% CI 1.75-4.35). Expression analysis using the Gene Expression Profiling Interactive Analysis database indicated that the expression of FEZF1-AS1 was higher in tumor tissues than that in the corresponding normal tissues. The results of survival analysis revealed that increased FEZF1-AS1 expression was correlated with poor OS and DFS in cancer patients. CONCLUSIONS: LncRNA FEZF1-AS1 may serve as a valuable prognostic biomarker for clinical outcomes in various solid tumors.

Calpain Small Subunit 1 Protein in the Prognosis of Cancer Survivors and Its Clinicopathological Correlation.

Background/Aims. Calpain small subunit 1 (Capn4) is implicated in tumorigenesis and plays a key role in multiple tumors. This study aimed to fully illustrate the prognostic value of Capn4 protein in cancer patients. METHODS: A systematic search was conducted against several online databases. Hazard ratios (HRs) or odds ratio (ORs) were used to investigate the relationship between Capn4 protein expression and prognosis as well as clinical parameters in cancer survivors. RESULTS: Eleven studies involving 1775 patients were identified. Overall, the results showed that Capn4 protein was associated with poor prognosis of overall survival (OS) (HR=1.74; 95% CI:1.47-2.01; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07; p<0.001) and event-free survival (EFS) (HR=1.73; 95% CI:1.39-2.07. CONCLUSIONS: Expression of Capn4 protein is associated with cancer survival and clinicopathologic characteristics in patients.