Procedures
tumor, death, toxicity, blood coagulation, Cancer
ADVERSE EVENT, TUMOR, DISEASE, ADVERSE EVENT, CPS, CANCER
This study enrolled 26 eligible patients with RM-NPC. The patients received 250 mg of apatinib orally once a day and camrelizumab 200 mg was injected intravenously once every two weeks until the disease progressed, intolerable toxicity appeared, the study was completed, or consent was withdrawn. Reduction of the dose of camrelizumab was not allowed. If the patient experienced a suspected immune related adverse event (AE), they could stop using camrelizumab temporarily or permanently, depending on the doctor’s judgment. Adjustments of the dose of apatinib were not permitted. Interruption of apatinib was allowed and was carried out according to the judgment of the therapist and local standard practice. If the dose of apatinib was interrupted, replenishment in subsequent cycles was not permitted, and if AEs greater than grade 3 occurred, treatment was discontinued.Each investigator (WJ, YFP, JZ, BZ, and YXS) assessed the tumor response in accordance with RECIST version 1.1. All patients underwent baseline examinations, including laboratory tests, magnetic resonance imaging (MRI), or computed tomography (CT), bone scan (bone scintigraphy), within 28 days after study inclusion. Laboratory tests were carried out every two weeks, which included renal function tests, liver function tests, and standard complete blood counts. Every 4 weeks, an electrocardiogram, routine stool and urine tests, blood coagulation tests, and thyroid function tests were reexamined. Imaging examination was performed every 6 weeks until the disease progressed or follow-up treatment began. According to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03), we recorded AEs during the trial, during treatment, and within 3 months after cessation of treatment. At the end of the study, patient follow-up was carried out every 4 weeks by telephone until death or the end of follow up. Efficacy analysis was performed in the intention-to-treat (ITT) population. Safety analyses were performed on all patients who received at least one dose of study treatment.Biomarker analyses employed blocks of paraffin-embedded tumor tissue taken from archival tumor tissue of the study participants. Immunohistochemical staining was performed after paraffin-embedded NPC tissue was cut into 5-µm-thick slides. The expression of PD-L1 was evaluated using a PD-L1 immunohistochemical kit (ab213524; Abcam, Cambridge, MA, USA) in the central laboratory. The comprehensive positive score (CPS) was used to report PD-L1 expression: CPS = (the number of PD-L1 positive tumor cells + the number of PD-L1 positive tumor associated immune cells)/the total number of tumor cells × 100. A CPS ≥ 1 indicated PD-L1 positivity. A primary antibody diluent was prepared using an antibody diluent (DAKO, Carpinteria, CA) containing background inducers and used for the following dilutions: anti-VEGFR-2 (ab115805, clone SP123,1:400; Abcam, Cambridge, UK); anti-CD4 (ab133616,1:800; Abcam); and anti-CD8 (ab245118,1:800; Abcam). Under light microscope, the whole section was randomly observed in 5 high power (10-40) visual fields, and the product of staining intensity and the percentage of positive cells was used as the judgment index. Finally, score of 0-7 was divided into low expression group, 8-12 was divided into high expression group. Real-time quantitative PCR was used to detect EBV DNA in plasma samples from patients. 400 copies/ml of plasma EBV DNA before treatment was taken as the critical value. A EBV DNA ≥ 400 copies/ml indicated EBV DNA positivity.