Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. Compared to the effect of placebo, it improved both progression-free survival (PFS) and overall survival (OS) in a phase III trial in patients with advanced non-small-cell lung cancer (NSCLC), despite progression of the cancer after two lines of prior treatments. Recently, the China Food and Drug Administration (CFDA) approved single agent anlotinib as a third-line treatment for patients with advanced NSCLC. Moreover, a randomized phase IIB trial demonstrated that anlotinib significantly prolonged the median PFS in patients with advanced soft tissue sarcoma (STS). Anlotinib also showed promising efficacy in patients with advanced medullary thyroid carcinoma and metastatic renal cell carcinoma (mRCC). The tolerability profile of anlotinib is similar to that of other tyrosine kinase inhibitors that target VEGFR and other tyrosine kinase-mediated pathways; however, anlotinib has a significantly lower incidence of grade 3 or higher side effects compared to that of sunitinib. We review the rationale, clinical evidence, and future perspectives of anlotinib for the treatment of multiple cancers.

IMPORTANCE One of the most recent treatment regimens used for hormone receptor (HR)positive, ERBB2 (formerly HER2)-negative metastatic breast cancer is treatment with the cyclindependent kinases 4 and 6 (CDK4/6) inhibitors and endocrine therapy (ET). OBJECTIVE To assess overall survival (OS), progression-free survival (PFS), objective response rate, and adverse events, especially grades 3 and 4 adverse events, among patients with HR-positive, ERBB2-negative metastatic breast cancer who were treated with CDK4/6 inhibitors plus ET vs ET alone. DATA SOURCES A systematic search of PubMed, Embase, the main oncology conference of the European Society of Medical Oncology, and the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium databases for randomized clinical trials of CDK4/6 inhibitors plus ET vs ET for HR-positive, ERBB2-negative metastatic breast cancer. Searches were performed up to March 30, 2020. STUDY SELECTION A total of 472 records were assessed in PubMed and Embase by 2 authors, including studies, international meeting reports, and reviews. Inclusion criteria were Englishlanguage phase 2 or 3 randomized clinical trials of HR-positive, ERBB2-negative metastatic breast cancer, with patients randomly assigned to receive CDK4/6 inhibitors plus ET or ET alone, and having OS or PFS outcomes. The exclusion criteria were phase 1 trials, retrospective studies, or studies without survival outcomes. Excluding the references, 16 articles were relevant. After excluding studies based on exclusion criteria, 9 studies were considered eligible for this meta-analysis. DATA EXTRACTION AND SYNTHESIS Two researchers independently extracted data and assessed potential bias. Data assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. The results were pooled using a fixed-effect model. MAIN OUTCOMES AND MEASURES Study heterogeneity was assessed using the I 2 statistic. Hazard ratios (HRs) and 95% CIs were used to evaluate PFS, OS, and subgroup analyses. Overall response and 95% CIs were used to evaluate the objective response rate and grade 3 or 4 adverse events. The primary outcome was OS. RESULTS In total, 9 studies that included a total of 5043 patients with metastatic breast cancer were assessed in this meta-analysis.

Background The role of capecitabine in neoadjuvant and adjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) is highly controversial. Our meta-analysis was designed to further elucidate the effects of capecitabine on survival in early-stage TNBC patients and its safety. Methods PubMed, Embase, and papers presented at several main conferences were searched up to December 19, 2019, to investigate capecitabine-based versus capecitabine-free neoadjuvant and adjuvant chemotherapy in TNBC patients. Heterogeneity was assessed using I2 test, combined with hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) computed for disease-free survival (DFS), overall survival (OS), and over grade 3 adverse events (AEs). Results A total of 9 randomized clinical trials and 3842 TNBC patients were included. Overall, the combined capecitabine regimens in neoadjuvant and adjuvant chemotherapy showed significantly improved DFS (HR = 0.75; 95% CI, 0.65–0.86; P < 0.001) and OS (HR = 0.63; 95% CI, 0.53–0.77; P < 0.001). In subgroup analysis, there were improvements in DFS in the groups with addition of capecitabine (HR = 0.64; 95% CI, 0.53–0.78; P < 0.001), adjuvant chemotherapy (HR = 0.73; 95% CI, 0.63–0.85; P < 0.001), and lymph node positivity (HR = 0.62; 95% CI, 0.44–0.86; P = 0.005). Capecitabine regimens were related to higher risks of diarrhea (OR = 2.88, 95% CI 2.23–3.74, P < 0.001), stomatitis (OR = 2.01, 95% CI 1.53–2.64, P < 0.001) and hand–foot syndrome (OR = 8.67, 95% CI 6.70–11.22, P < 0.001). Conclusion This meta-analysis showed that neoadjuvant and adjuvant chemotherapy combined with capecitabine significantly improved both DFS and OS in early-stage TNBC patients with tolerable AEs. There were benefits to DFS in the groups with the addition of capecitabine, adjuvant chemotherapy, and lymph node positivity.

No abstract

BackgroundChemotherapy can improve the survival of patients with advanced gastric cancer. However, whether triplet chemotherapy can further improve the survival of patients with advanced gastric cancer compared with doublet chemotherapy remains controversial. This study reviewed and updated all published and eligible randomized controlled trials (RCTs) to compare the efficacy, prognosis, and toxicity of triplet chemotherapy with doublet chemotherapy in patients with advanced gastric cancer.MethodsRCTs on first-line chemotherapy in advanced gastric cancer on PubMed, Embase, and the Cochrane Register of Controlled Trials and all abstracts from the annual meetings of the European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology conferences up to October 2018 were searched. The primary outcome was overall survival, while the secondary outcomes were progression-free survival (PFS), time to progress (TTP), objective response rate (ORR), and toxicity.ResultsOur analysis included 23 RCTs involving 4540 patients and 8 types of triplet and doublet chemotherapy regimens, and systematic review and meta-analysis revealed that triplet chemotherapy was superior compared with doublet chemotherapy in terms of improving median OS (HR = 0.92; 95% CI, 0.86–0.98; P = 0.02) and PFS (HR = 0.82; 95% CI, 0.69–0.97; P = 0.02) and TTP (HR = 0.92; 95% CI, 0.86–0.98; P = 0.02) and ORR (OR = 1.21; 95% CI, 1.12–1.31; P < 0.0001) among overall populations. Compared with doublet chemotherapy, subgroup analysis indicated that OS improved with fluoropyrimidine-based (HR = 0.80; 95% CI, 0.66–0.96; P = 0.02), platinum-based (HR = 0.75; 95% CI, 0.57–0.99; P = 0.04), and other drug-based triplet (HR = 0.79; 95% CI, 0.69–0.90; P = 0.0006) chemotherapies while not with anthracycline-based (HR = 0.70; 95% CI, 0.42–1.15; P = 0.16), mitomycin-based (HR = 0.81; 95% CI, 0.47–1.39; P = 0.44), taxane-based (HR = 0.91; 95% CI, 0.81–1.01; P = 0.07), and irinotecan-based triplet (HR = 1.01; 95% CI, 0.82–1.24; P = 0.94) chemotherapies. For different patients, compared with doublet chemotherapy, triplet chemotherapy improved OS (HR = 0.89; 95% CI, 0.81–0.99; P = 0.03) among Western patients but did not improve (HR = 0.96; 95% CI, 0.86–1.07; P = 0.47) that among Asian patients.ConclusionsCompared with doublet chemotherapy, triplet chemotherapy improved OS, PFS, TTP, and ORR in patients with advanced gastric cancer in the population overall, and improved OS in Western but not in Asian patients.