Objective Anlotinib, an oral small-molecular tyrosine kinase inhibitor (TKI) on tumor angiogenesis and growth, has a wide spectrum of inhibitory effects on targets such as vascular endothelial growth factor receptors 2/3 (VEGFR2/3), etc. The efficacy and safety of anlotinib in the treatment of platinum-resistant or platinum-refractory ovarian cancer were evaluated. Patients and Methods Patients with platinum-resistant or platinum-refractory ovarian cancer that treated with anlotinib in the Affiliated Cancer Hospital of Zhengzhou University from May 2018 to March 2020 were included. Medical records were reviewed in terms of objective response, survival outcomes, and safety. Results A total of 38 patients were analyzed. The median progression-free survival and the median overall survival were 7.7 months (95% CI: 6.7–8.7) and 16.5 months (95% CI: 13.3–19.7), respectively. About 17 patients received anlotinib monotherapy, and the median progression-free survival was 7.7 months (95% CI: 6.3–9.1). A total of 19 cases received anlotinib plus chemotherapy with a median progression-free survival of 8.0 months (95% CI: 4.8–11.2). A total of 2 cases received anlotinib plus anti-PD-1 antibody pembrolizumab, and 1 case had partial response, the other progressive disease. The objective response rate was 42.1% while the disease control rate was 86.8%. A total of 5 patients experienced dose reduction from 12 mg to 10 mg because of adverse effects. The most common adverse effects were hypertension (31.6%), fatigue (28.9%), anorexia (26.3%) and hand-foot syndrome (23.7%). No treatment-related deaths were recorded. Conclusion Anlotinib produced moderate improvements in progression-free survival and overall survival in patients with platinum-resistant or platinum-refractory ovarian cancer. It indicates that anlotinib maybe a new treatment option for patients with platinum-resistant or platinum-refractory ovarian cancer.
At present, treatment options for osimertinib resistance are very limited. Dual inhibition of the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) significantly improved the progression-free survival (PFS) of advanced EGFR-mutant non–small cell lung cancer (NSCLC). After EGFR-tyrosine kinase inhibitor (TKI) resistance, EGFR-TKI continuation combined with VEGF inhibitors still had clinical benefits. It is unclear whether the addition of bevacizumab after osimertinib progresses will prolong the duration of the osimertinib benefit. We screened 1289 patients with NSCLC and finally included 96 patients to evaluate osimertinib combined with bevacizumab (osi + bev) versus chemotherapy combined with bevacizumab (che + bev) for patients with acquired resistance to osimertinib. The overall response rate (ORR) for osi + bev and chem + bev was 15.8% (6 of 38) and 20.7% (12 of 58), respectively. The median PFS for osi + bev and che + bev was 7.0 and 4.9 months (HR 0.415 95%CI: 0.252–0.687 p = 0.001). The median OS for osi + bev and che + bev was 12.6 and 7.1 months (HR 0.430 95%CI: 0.266–0.696 p = 0.001). Multivariate analyses showed that no brain metastases and osi + bev treatment after osimertinib resistance correlated with longer PFS (p = 0.044, p = 0.001), while the median PFS of osimertinib less than 6 months (p = 0.021) had a detrimental effect on sequent treatment. Only osi + bev treatment was identified as an independent predictor of OS (p = 0.001). The most common adverse events (AEs) of grade ≥3 were hypertension (13.2%) and diarrhea (10.5%) in the osi + bevacizumab group. Neutropenia (24.1%) and thrombocytopenia (19%) were the most common grade ≥3 AEs in the che + bev group. The overall incidence of serious AEs (grade ≥3) was significantly higher in the chemotherapy plus bevacizumab group. Our study has shown the superiority of osi + bev compared to che + bev after the failure of osimertinib, making it a preferred option for patients with acquired resistance to osimertinib.
AETC has significant effects on the growth of A549 xenografts and on the activity of the EGFR/MAPK pathway. Therefore, AETC may be beneficial in lung carcinoma treatment.
BackgroundBoth apatinib and programmed death 1 (PD-1) monoclonal antibody (mAb) monotherapy have been licensed in China for the third-line treatment of advanced gastric cancer (AGC). However, whether the combination could improve the prognosis of patients with AGC after second-line treatment has not been evaluated.MethodsWe retrospectively screened 892 patients with AGC who received third-line or later treatment from June 2016 to July 2021 at the Affiliated Cancer Hospital of Zhengzhou University and second People’s Hospital of Pingdingshan. 166 patients who received apatinib plus PD-1 mAb, apatinib, or PD-1 mAb were included. Based on medical records and follow-up data, we analyzed the efficacy and safety of these three treatment options.ResultsPatients received apatinib plus PD-1 mAb (n=49), apatinib monotherapy (n=63), or PD-1 mAb monotherapy (n=54). Apatinib plus PD-1 mAb showed significantly longer progression-free survival (PFS) and overall surivival (OS) compared with the apatinib monotherapy (PFS: 5.5 months versus 3.0 months; p=0.002; OS: 10 months versus 7.6 months; p=0.011) or PD-1 mAb monotherapy (PFS: 5.5 months versus 2.3 months; p=0.017; OS: 10 months versus 6.5 months; p=0.004). Apatinib plus PD-1 mAb showed higher ORR and DCR than the apatinib and PD-1 mAb monotherapy (ORR: 34.7% versus 6.3% versus 9.3%; p=0.001; DCR: 75.5% versus 44.4% versus 40.7%; p=0.001). Further subgroup analysis for PFS and OS shown consistent efficacy in most subgroups with apatinib plus PD-1 mAb versus apatinib monotherapy or PD-1 mAb monotherapy. Multivariate analyses suggested that apatinib plus PD-1 mAb was significantly associated with better PFS and OS. Most of the treatment-related toxicities were mild and tolerable.ConclusionCompared with the monotherapy of either apatinib or PD-1 mAb, apatinib plus PD-1 mAb treatment yielded longer PFS and OS, and achieved significant higher ORR and DCR.
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