Adjunctive PD-1 inhibitor standard chemotherapy in recurrent or metastatic nasopharyngeal carcinoma: a systematic review and meta-analysis

Objective: To investigate whether Adjunctive PD-1 inhibitors have improved clinical outcomes compared to chemotherapy alone in platinum-pretreated and platinum-naive recurrent or metastatic nasopharyngeal carcinoma (R/M NPCA). Methods: The study involved a literature search from PubMed, Cochrane CENTRAL, and Google Scholar for randomized clinical trials (RCTs) on the use of PD-1 inhibitors versus chemotherapy alone in patients with R/M NPCA. Bias was assessed using Cochrane collaboration’s risk of bias tool. Overall Survival (OS) was examined as the primary endpoint. Secondary endpoints were Progression-Free Survival (PFS), Objective Response Rate, Disease Control Rate (DCR), Duration of Response, and Serious/Grade ⩾3 Adverse Events. Outcomes were measured with either Mean Difference, Risk ratio (RR), or Hazard ratios (HRs) at 95% confidence interval. Results: Four RCTs were included in the meta-analysis and systematic review. OS for the monotherapy subgroup was a HR of 0.87 [0.67, 1.13] ( p = 0.30) while the combination subgroup had 0.64 [0.45, 0.90] ( p = 0.01). The monotherapy subgroup exhibited significantly worse outcomes in PFS (HR 1.31 [1.01, 1.68]) ( p = 0.04) and DCR (RR 1.52 [1.12, 2.05]) ( p = 0.007) but no significant difference in other outcomes. For combination therapy, a statistically significant benefit can be seen in all outcomes except DCR (RR 0.62 [0.38, 1.01]) ( p = 0.06) which was a non-significant benefit favoring PD-1 inhibitors. Conclusion: Combination PD-1 inhibitor + chemotherapy followed by maintenance PD-1 inhibitor therapy is superior to chemotherapy alone in the first-line treatment of R/M NPCA, implying a potential benefit with the use of PD-1 inhibitors + chemotherapy with maintenance PD-1 inhibitors as first-line in R/M NPCA compared to standard chemotherapy alone.