Purpose: The role of chemotherapy has evolved greatly in advanced nasopharyngeal carcinoma (NPC). We undertook this network meta-analysis to establish the optimal chemotherapy strategy in advanced NPC.
Materials and methods:
 This network meta-analysis recruited randomized clinical trials involving patients with advanced NPC randomly allocated to induction chemotherapy plus concurrent chemoradiotherapy (CRT; induction + CRT), CRT plus adjuvant chemotherapy (CRT + adjuvant), CRT or radiotherapy (RT) alone. Pairwise meta-analysis was first conducted, then network meta-analysis was performed using the frequentist approach. Effect size was expressed as HR and 95% CI.
Results:
 In total, we analyzed 15 studies involving 4,067 patients with 880 (21.6%) patients receiving induction + CRT, 897 (22.1%) receiving CRT + adjuvant, 1,421 (34.9%) receiving CRT, and 869 (21.4%) receiving RT alone. Induction + CRT achieved significantly better distant failure-free survival (HR, 0.67; 95% CI, 0.53–0.86) and locoregional failure-free survival (HR, 0.69; 95% CI, 0.54–0.89) than CRT, and CRT + adjuvant achieved better overall survival than CRT (HR, 0.82; 95% CI, 0.67–1.00). However, no significant survival difference was found between the induction + CRT and CRT + adjuvant groups. Additionally, RT alone is always worse than the other three treatments. In terms of P-score, induction + CRT ranked best for distant and locoregional failure-free survival, while CRT + adjuvant ranked best for overall survival.
Conclusion: Both induction + CRT and CRT + adjuvant were equally effective and feasible choices for patients with advanced NPC.
Keywords:
 nasopharyngeal carcinoma, advanced, concurrent chemoradiotherapy, induction chemotherapy, adjuvant chemotherapy, network meta-analysis

INTRODUCTION

Nasopharyngeal carcinoma (NPC), known as a special kind of head and neck malignancy, is mainly prevalent in East Asia and South China while its incidence in white population is extremely low.1According to the recent data on cancer epidemiology, NPC has emerged as the most common head and neck cancer in China.2,3 Radiotherapy (RT) is the only radical therapy for nonmetastatic disease as a result of complicated anatomy location and high radiation sensitivity of NPC. Also, NPC is highly sensitive to chemotherapy and combined RT with chemotherapy is essential for advanced disease.

The role of chemotherapy in advanced NPC was first established by the Intergroup 0099 study, which revealed concurrent prevalent (CRT) plus adjuvant chemotherapy achieved better overall survival (OS) than RT alone.4 Later on, many validated trials that were carried out in Asia further strengthen the role of CRT plus adjuvant chemotherapy in NPC.5–7 However, a randomized phase III clinical trial by Chen et al demonstrated that adjuvant chemotherapy additional to CRT may be useless.8 Consequently, CRT with or without adjuvant chemotherapy has been recommended as the standard treatment for advanced NPC. Although these achievements have been made, the prognosis of advanced disease still remains poor.9 Therefore, scientists evaluated the efficacy and toxicity of induction chemotherapy additional to CRT in advanced NPC. Thankfully, recent studies found that induction chemotherapy plus CRT was superior to CRT alone,10–14 making induction chemotherapy a promising treatment for advanced NPC. However, another clinical issue produced: what is the best treatment in advanced NPC? Induction chemotherapy plus CRT (induction + CRT) or CRT plus adjuvant chemotherapy (CRT + adjuvant)? To date, no head-to-head clinical study comparing induction + CRT with CRT + adjuvant has been reported. A network meta-analysis employing individualized patient data (IPD) compared these two treatments indirectly and found no significant difference.15 Notably, many recent studies were not included in this meta-analysis. Thus, it is worth reanalyzing this issue using the updated data. Given this concern, we conducted this network meta-analysis to establish the optimal treatment in advanced NPC.