PurposeThe current study was carried out to compare the effectiveness and safety of different ALK inhibitors in treating ALK+ NSCLC.MethodsProgression‐free survival (PFS), disease control rate (DCR), overall response rate (ORR), and intracranial ORR and DCR have been aggregated to appraise the effectiveness of each ALKi. The discontinuation rate due to adverse events (AEs) was pooled to evaluate their safety. Bayesian network meta‐analyses were used to compare the ORR, DCR, PFS, and discontinuation rate of patients treated with alectinib, ceritinib, crizotinib, and chemotherapy.ResultsCompared with chemotherapy, ALK inhibitors significantly prolonged PFS [hazard ratio (HR) and 95% confidence interval (CI): alectinib, 0.50 (0.43‐0.58); ceritinib, 0.75 (0.69‐0.83); crizotinib, 0.71 (0.66‐0.76)]. The ORRs were significantly higher for ALK inhibitors than for chemotherapy [odds ratio (OR) and corresponding 95% CI: alectinib, 11.69 (4.29‐36.56); ceritinib, 7.85 (3.44‐19.27); crizotinib, 6.04 (3.33‐11.71)]. The discontinuation rates were lower for ALK inhibitors than for chemotherapy [OR and corresponding 95% CI: alectinib, 0.42 (0.12‐1.36); ceritinib, 0.52 (0.20‐1.35); crizotinib, 0.70 (0.30‐1.62)].Conclusions ALK+ NSCLC patients treated with ALKi tend to have longer PFS than those treated with chemotherapy. ALKi‐naïve patients tended to response better than their ALKi‐pretreated counterparts. Alectinib appeared to be preferable for treating brain metastases due to its high intracranial efficacy. Patients treated with alectinib or ceritinib tended to have higher ORR and DCR than patients with similar baselines treated with crizotinib or chemotherapy. No significant differences in discontinuation rate were found for alectinib, ceritinib, crizotinib, and chemotherapy.

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BackgroundAlectinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor approved by the US Food and Drug Administration to treat crizotinib-refractory non-small cell lung cancer. We performed this meta-analysis to synthesize the results of different clinical trials to evaluate the efficacy and safety of alectinib.MethodsA search of 3 databases, including PubMed, Web of Science, and the Cochrane Library, was performed from the inception of each database through September 5, 2017. We have pooled the overall response rate (ORR), disease control rate, progression-free survival, and intracranial ORR to evaluate the efficacy of alectinib. Discontinuation rate, rate of dose reduction or interruption due to adverse events as well as the incidence of several adverse events were aggregated to evaluate its safety.ResultsA total of 8 studies with 626 patients have been included in our study. The pooled efficacy parameters are as follows: ORR 70% (95% CI: 57% to 82%), disease control rate 88% (95% CI: 82% to 94%), progression-free survival 9.36 months (95% CI: 7.38% to 11.34%), and intracranial ORR 52% (95% CI: 45% to 59%). ALK inhibitor-naïve patients tend to have better responses than crizotinib-pretreated patients. The aggregate discontinuation rate is 7% (95% CI: 4% to 10%), and the pooled rate of dose reduction or interruption is 33% (95% CI: 24% to 42%). The incidences of most adverse events were relatively low, while the incidences of 2 frequently reported adverse events, myalgia (18%) and anemia (25%), were even higher than with the first-generation ALK inhibitor crizotinib.ConclusionGenerally, alectinib is a drug with preferable efficacy and tolerable adverse effects, and it is suitable for the treatment of intracranial metastases.

Objective: Cell division cycle 25C (CDC25C) is involved in the regulation of the G2/M phase transition and is associated with various cancers, including non-small cell lung cancer. We evaluated its prognostic value in lung adenocarcinoma (LUAD) based on data from The Cancer Genome Atlas (TCGA).Methods: Kruskal-Wallis test, Wilcoxon signed-rank test, and logistic regression were used to evaluate relationships between clinical-pathologic features and CDC25C expression. Cox regression analyses and the Kaplan-Meier method were used to evaluate factors contributing to prognosis. Gene set enrichment analysis (GSEA) was performed.Results: High CDC25C expression in LUAD was associated with a high tumor extent (odds ratio (OR) = 2.23 (1.52-3.29), P < 0.001), regional lymph node invasion (OR = 2.18 (1.48-3.22), P < 0.001), OR = advanced stage (OR = 2.47 (1.72-3.59), P < 0.001), and poor status (OR = 1.87 (1.19-2.96), P = 0.007). A univariate analysis showed that high CDC25C expression is associated with a short overall survival (OS) (HR: 1.873; 95% CI: 1.385-2.535; P < 0.001) and poor progression-free survival (HR: 1.503; 95% CI: 1.173-1.926; P = 0.0012). In a multivariate analysis, high CDC25C expression was associated with poor OS (HR = 2.193; CI: 1.394-3.452, P = 0.001). GSEA showed the enrichment of cell cycle, apoptosis, p53-dependent G1 DNA damage response, S-phase, mitotic M-M G1 phases, and FA-mediated cell death in the CDC25C high-expression phenotype.Conclusions: CDC25C predicts poor prognosis in LUAD and may function in cell cycle regulation and FAS-mediated apoptosis.