What Is the Best Treatment of Locally Advanced Nasopharyngeal Carcinoma? An Individual Patient Data Network Meta-Analysis

Abstract

Purpose The role of adjuvant chemotherapy (AC) or induction chemotherapy (IC) in the treatment of locally advanced nasopharyngeal carcinoma is controversial. The individual patient data from the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma database were used to compare all available treatments. Methods All randomized trials of radiotherapy (RT) with or without chemotherapy in nonmetastatic nasopharyngeal carcinoma were considered. Overall, 20 trials and 5,144 patients were included. Treatments were grouped into seven categories: RT alone (RT), IC followed by RT (IC-RT), RT followed by AC (RT-AC), IC followed by RT followed by AC (IC-RT-AC), concomitant chemoradiotherapy (CRT), IC followed by CRT (IC-CRT), and CRT followed by AC (CRT-AC). P-score was used to rank the treatments. Fixed- and random-effects frequentist network meta-analysis models were applied. Results The three treatments with the highest probability of benefit on overall survival (OS) were CRT-AC, followed by CRT and IC-CRT, with respective hazard ratios (HRs [95% CIs]) compared with RT alone of 0.65 (0.56 to 0.75), 0.77 (0.64 to 0.92), and 0.81 (0.63 to 1.04). HRs (95% CIs) of CRT-AC compared with CRT for OS, progression-free survival (PFS), locoregional control, and distant control (DC) were, respectively, 0.85 (0.68 to 1.05), 0.81 (0.66 to 0.98), 0.70 (0.48 to 1.02), and 0.87 (0.61 to 1.25). IC-CRT ranked second for PFS and the best for DC. CRT never ranked first. HRs of CRT compared with IC-CRT for OS, PFS, locoregional control, and DC were, respectively, 0.95 (0.72 to 1.25), 1.13 (0.88 to 1.46), 1.05 (0.70 to 1.59), and 1.55 (0.94 to 2.56). Regimens with more chemotherapy were associated with increased risk of acute toxicity. Conclusion The addition of AC to CRT achieved the highest survival benefit and consistent improvement for all end points. The addition of IC to CRT achieved the highest effect on DC.

Fig 1.

Graphical representation of the trial network for overall and progression-free survival. The size of the nodes is proportional to the number of patients (pts), which is given in parenthesis in each treatment category. The width of the lines is proportional to the number of comparisons. The number of trials (t) and pts in each comparison are displayed next to each line. The network included 26 comparisons from 20 trials. Six comparisons were counted for the QMH-95 trial (2 × 2 design) and two for the NPC-9902 trial (2 × 2 design; second randomization on radiotherapy [RT] modalities). Because of the duplication of QMH-95 trial arms, some pts are counted multiple times in this figure (in the RT, concomitant chemoradiotherapy [CRT], CRT-adjuvant chemotherapy [AC], and RT-AC groups). However, the statistical analysis takes into account the correlation structure in this design and does not give an excessive weight to duplicated patients. IC, induction chemotherapy.

Fig 2.

Forest plot for overall survival (on the left) and progression-free survival (on the right), showing results from direct comparisons and network meta-analysis. HR < 1 is in favor of the first treatment mentioned in the title (ie, IC-RT for the comparison IC-RT v RT). Only comparisons involving two trials or more are presented here. For comparisons with only one trial, the hazard ratios used are reported in the Data Supplement. AC, adjuvant chemotherapy; CRT, concomitant chemoradiotherapy; HR, hazard ratio; IC, induction chemotherapy; RT, radiotherapy;