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PURPOSE: To investigate the efficacy of metastasis-directed therapy (MDT) when added to camrelizumab (Cam) in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). METHODS: We conducted a randomised, controlled, multicentre, phase II trial in 3 centres from China (NCT04830267). Patients with R/M-NPC, without prior exposure to immunotherapy, who presented with ≥2 lesions, and at least 1 measurable lesion were randomised 1:1 to either Cam alone or Cam plus MDT (Cam+MDT). Patients randomised to the MDT group must have 1 lesion that is amendable to stereotactic body radiotherapy (SBRT) prescribed to 27Gy in 3 fractions every other day. Primary endpoint was objective response rate (ORR) of unirradiated lesions by RECIST v1.1. RESULTS: Between April 2021 and August 2023, 39 patients were randomly assigned to receive either Cam (n=20) or Cam+MDT (n=19). 17/39 (43.6%) patients had oligometastatic disease (≤3 lesions); 18/39 (46.2%) had liver involvement; 3/39 (7.7%) had locoregional recurrent disease. ORR of unirradiated lesions did not differ between the treatment groups (26.3% [Cam+MDT] vs 30.0% [Cam], P=1.0). DCR of unirradiated lesions was 73.7% in the Cam+MDT group compared with 60.0% in the Cam group (P=0.571). After a median follow-up of 25.8 months, median progression-free survival was 9.3 (95% CI: 6.2-NR) months in the Cam+MDT group and 8.8 (95% CI: 3.3-NR) months in the Cam group (P=0.750). Exploratory analyses suggested a longer overall survival (OS) with Cam+MDT for patients with >3 lesions (HR 0.23 [95% CI: 0.07-0.77], P=0.009). G3 and above adverse events were comparable between the treatment groups (15.8% [Cam+MDT] vs 20.0% [Cam]). Overall rate of capillary proliferation was 17.9% (7/39) on the trial. CONCLUSIONS: Our study did not meet its primary endpoint of superior ORR of unirradiated lesions with the addition of MDT to Cam in patients with R/M-NPC.
RESUMO
OBJECTIVES: To characterize longitudinal changes in Epstein-Barr virus (EBV) DNA post-radiotherapy in nasopharyngeal carcinoma (NPC) patients, and investigate whether an early (0-2 weeks) or delayed (8-12 weeks) EBV DNA result better predicts for disease-free survival (DFS). MATERIALS AND METHODS: Histologically-confirmed NPC patients with ≥1 EBV DNA test quantified using the harmonized BamHI-W polymerase chain reaction-based assay at 0-2 and 8-12 weeks post-radiotherapy were included. RESULTS: We identified 302 patients with EBV DNA measured at 0-2 weeks post-radiotherapy; of which, 110 (36.4 %) underwent a repeat test at 8-12 weeks post-treatment. Patients harboring a detectable EBV DNA at 0-2 weeks experienced an inferior DFS (adjusted HR1-264 copies 1.72 [95 %CI: 1.05-2.83], P = 0.031; AHR≥265 copies 4.39 [95 %CI: 1.68-11.44], P = 0.002 relative to 0 copies/mL). At 8-12 weeks, we observed substantial shifts in EBV DNA readings from 0 to 2 weeks; 76/110 (69.1 %) and 34/110 (30.9 %) patients at 0-2 weeks versus 90/110 (81.8 %) and 20/110 (18.2 %) at 8-12 weeks recorded undetectable and detectable EBV DNA, respectively. Positive EBV DNA at 8-12 weeks was strongly associated with relapse (73.3 % [11/15] for 1-264; 80.0 % [4/5] for ≥265 subgroups had relapses versus 15.6 % [14/90] for 0 copies/mL). Area under receiver operating curve values for 2-year relapse rates were 0.817 (95 %CI: 0.725-0.909) for stage + EBV DNA8-12w versus 0.654 (95 %CI: 0.542-0.765) for stage + EBV DNA0-2w. CONCLUSION: EBV DNA is dynamic post-radiotherapy, and delayed EBV DNA testing better enriched for higher-risk NPC patients. This implicates trials investigating adjuvant chemotherapy intensification based on early EBV DNA testing.