Neoadjuvant chemotherapy plus concomitant chemoradiation versus concomitant chemoradiation for locoregionally advanced nasopharyngeal carcinoma: A systematic review and meta-analysis of comparative studies.

Abstract

e17552 Background: To determine if addition of neoadjuvant chemotherapy (NACT) to concomitant chemoradiation (CCRT) for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) improves overall survival. Methods: We searched MEDLINE for eligible studies comparing NACT plus CCRT versus (vs) CCRT alone for locoregionally advanced NPC. We assessed the methodological quality of the included studies using the MERGE criteria. We performed the meta-analysis with random effects model using Revman 5.3 to estimate the pooled hazard ratios (HR), confidence intervals (CI), P values (P) and I squared statistic (I2). The primary outcome was overall survival (OS); secondary outcomes include progression-free survival (PFS) and adverse events (AE). We used the GRADE approach to appraise the quality of evidence from randomized trials. Results: We found four randomized and five retrospective comparative studies including 2178 patients with low to moderate risk of bias in their methodologic quality. Pooled estimates from both randomized and retrospective studies demonstrated a benefit in PFS (HR 0.78, 95% CI 0.66 to 0.93, P = 0.006, I2 = 0%) and OS (HR 0.77, 95% CI 0.61 to 0.96, P = 0.02, I2 = 0%) with NACT. In the randomized trials, there was moderate quality evidence that NACT improved PFS significantly (HR 0.73, 95% CI 0.57 to 0.93, P = 0.01, I2 = 0%); trend towards OS benefit (HR 0.76, 95% CI 0.56 to 1.03, P = 0.08, I2= 0%) and was associated with more frequent AE. There were no significant differences in the results between the randomized and retrospective comparative studies (PFS HR 0.73 vs 0.82, interaction P (IP) = 0.58; OS HR 0.76 vs 0.78, IP = 0.93). Conclusions: Neoadjuvant chemotherapy delays disease progression substantially and may improve survival for locoregionally advanced nasopharyngeal carcinoma. There were no divergent results between randomized and retrospective comparative studies. Future trials should test more effective and/or better tolerated agents during the neoadjuvant therapy phase.