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Introduction: The effect of icotinib on non-small cell lung cancer (NSCLC) patients with EGFR exon 19 deletions (19-Del) or L858R point mutation in exon 21 (21-L858R) remains inconsistent. This study aimed to evaluate the efficacy and safety of icotinib in patients with advanced NSCLC harboring these 2 EGFR mutations. Methods: We retrospectively assessed the clinical effects of first-line icotinib on advanced NSCLC patients with 2 classic EGFR mutations. Kinase activity assays were used to reaffirm the preclinical efficacy. Results: Among 2,757 patients, 2,365 (86%) harbored 19-Del (1,346/2,757, 49%) or 21-L858R (1,019/2,757, 37%) mutation. Patients with 19-Del had a higher response rate (ORR; 67.8 vs. 62.1%; p = 0.0039) and disease control rate (98.5 vs. 97.2%; p = 0.0223) than those with 21-L858R mutation. The median progression-free survival (PFS) in the 19-Del group (22.3 months, 95% confidence interval [CI]: 21.3–23.4) was significantly longer than that in the 21-L858R group (20.4 months, 95% CI: 19.5–21.7) (p = 0.004). In multivariate analysis, mutation types, clinical stage, and smoking history were significant factors for PFS. Additionally, an in vitro study indicated the 50% inhibitory concentrations (IC50) of icotinib was lower for EGFR 19-Del than 21-L858R. Conclusion: These results suggest that EGFR 19-Del confers superior PFS and response to the icotinib treatment compared to 21-L858R. [ABSTRACT FROM AUTHOR]

Background: Ensartinib is a potent new-generation ALK inhibitor with high activity against a broad range of known crizotinib-resistant ALK mutations and CNS metastases. We aimed to assess the efficacy and safety of ensartinib in ALK-positive patients with non-small-cell lung cancer (NSCLC), in whom crizotinib therapy was unsuccessful. The associations between ensartinib efficacy and crizotinib-resistant mutations were also explored., Methods: We did a single-arm, open-label, phase 2 study at 27 centres in China. Patients were aged 18 years or older, had stage IIIb or stage IV ALK-positive NSCLC that had progressed while they were on crizotinib therapy, an Eastern Cooperative Oncology Group performance status of 2 or less, had measurable disease, and had received fewer than three previous treatments. Patients with CNS metastases were included if these metastases were asymptomatic and did not require steroid therapy. All patients received 225 mg ensartinib orally once daily on a continuous dosing schedule. The primary outcome was the proportion of patients with an objective response according to the Response Evaluation Criteria in Solid Tumors (version 1.1), as assessed by an independent review committee in all patients who received at least one dose of ensartinib with no major violations of the inclusion criteria (ie, the full analysis set). Safety was assessed in all enrolled patients who received at least one dose of ensartinib. This trial was registered with ClinicalTrials.gov, NCT03215693., Findings: Between Sept 28, 2017, and April 11, 2018, 160 patients were enrolled and had at least one dose of ensartinib (safety analysis set). Four patients had inclusion violations and were excluded from the efficacy analysis, which thus included 156 patients (full analysis set). 97 (62%) patients in the full analysis set had brain metastases. 76 (52% [95% CI 43-60]) of 147 patients in the full analysis set, with responses that could be assessed by the independent review committee, had an objective response. 28 (70% [53-83]) of 40 patients with measurable brain metastases as assessed by the independent review committee had an intracranial objective response. 145 (91%) of 160 patients had at least one treatment-related adverse event, which were mostly grade 1 or 2. The most common treatment-related adverse events were rash (89 [56%]), increased alanine aminotransferase concentrations (74 [46%]), and increased aspartate aminotransferase concentrations (65 [41%])., Interpretation: Ensartinib has activity and is well tolerated in patients with crizotinib-refractory, ALK-positive NSCLC, including those with brain metastases. The role of ensartinib in patients in whom other second-generation ALK inhibitors have been unsuccessful warrants further studies., Funding: Betta Pharmaceuticals., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: RCC is the most common solid renal malignancy in adults worldwide. To provide the insight of clinicopathologica epidemiological characteristics and change tendencies of renal cell carcinoma (RCC), 2154 cases were collected from Shanxi Province of China, including diagnose time, age, gender, tumor size, Fuhrman grade, tumor stage, tumor location, local advance or distant metastasis and first symptom from 2005 to 2014. This retrospectively investigation, as its general objective, was to analyze the clinicopathologica epidemiological characteristics and the change tendencies of RCC., Methods: Between 2005 and 2014, 2154 patients who were diagnosed with RCC in three large tertiary hospitals at Shanxi Province were included. The patients' demographic features, pathological diagnoses and metastatic statuses were analyzed. Statistics methods include the chi-squared test, analysis of variance, Spearman's correlation analysis, Logistic regression and ARIMA modeling., Results: Of the 2154 included patients, the constituent ratio of female /male was 63.1% and 36.9%, with the median age of 57 years old. Fuhrman grade distributions differed significantly between males and females (p = 0.024). Also, a significant difference in tumor size was found by different clinical stages (p < 0.001), with a linear correlation (p < 0.001). Moreover, Spearman's analysis indicated tumor grade has a negative correlation with female (p = 0.009) and a positive correlation with tumor size (p = 0.000). It was found that the tumor diameter is bigger in the left side (p = 0.022). Furthermore, the metastasis rate was higher in the bigger tumor (p < 0.001) and the left-sided tumors (p = 0.027). Logistic regression also showed that tumor size is a risk factor for metastasis (OR = 1.724). The risk of local advance or distant metastasis in the left kidney was 1.6-fold greater than that of the right kidney. From 2005 to 2014 the number of RCC cases gradually increased (mainly for pathological grade II and III, but grade I and IV), while the average tumor size decreased, showing the severity increase mildly. Base on the results of a time series analysis-prediction the average RCC size would continue to decrease from the first quarter of 2015 to the fourth quarter of 2016., Conclusions: The cases of RCC increased from 2005 to 2014 with clear cell type as the main pathological type in this population. The characteristics in the constituent ratios of the RCC vary depending on gender, pathological grade, tumor size, and location, which may be the important factors impacting treatment and prognosis.