Discussion
toxicity, tumor, soft-tissue sarcoma
NON-SMALL CELL LUNG CANCER, DISEASE PROGRESSION, TUMOR, INFILTRATION, ORAL MUCOSITIS, DISEASE, MEDULLARY THYROID CARCINOMA
In this trial, RM-NPC patients who received anlotinib monotherapy as third-line or further therapy demonstrated effective disease control and acceptable toxicity profile. Subgroup analysis identified plasma EBV DNA levels and HFS as prognostic factors of treatment response. The findings support further clinical development of anlotinib for RM-NPC patients who have dismal survival outcomes and limited treatment options.Several antiangiogenic MKIs had been studied in RM-NPC (Additional file In this study, patients with prior anti-PD-1 immunotherapy tended to have higher therapeutic efficacy to anlotinib treatment, especially for patients who finished anti-PD-1 immunotherapy less than 3 months before anlotinib treatment. This may be because the anti-tumor immunity remains activated in the short term after the end of immunotherapy, while antiangiogenic drugs could further increase the infiltration of immune effector cells in the tumor microenvironment by normalizing immature blood vessels [Grade 3/4 HFS and oral mucositis observed in this trial were more common than previously reported for anlotinib monotherapy in patients with advanced non-small cell lung cancer, soft-tissue sarcoma, and medullary thyroid carcinoma [In this trial, high baseline EBV DNA copy number (≥ 1000 IU/mL) and increase from baseline in EBV DNA level were all associated with higher rate of disease progression during the anlotinib treatment. In the pilot study of single-agent apatinib treatment in RM-NPC patients, low baseline EBV DNA level was associated with long-term response, while change of EBV-DNA level after apatinib treatment was not correlated with the duration of response [The study has several limitations. First, this is a single-arm study in the absence of a control group. Second, the results of dynamic monitoring of EBV DNA copy numbers were not available in all enrolled patients. Thirdly, the results of our subgroup analysis may be limited by the small cohort size. Finally, only Han Chinese subjects were included in the trial. The efficacy and safety of anlotinib should be evaluated in NPC patients of diverse ethnicities across countries in the future.