Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: A phase III multicentre randomised controlled trial.

6005 Background: The role of neoadjuvant chemotherapy (NACT) for locoregionally advanced nasopharyngeal carcinoma (NPC) is unclear. We aimed to evaluate the feasibility and efficacy of NACT followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in locoregionally advanced NPC. Methods: Patients with stage III-IVB (excluding T3N0-1) NPC were randomly assigned to receive NACT followed by CCRT (investigational arm) or CCRT alone (control arm). Both arms were treated with 80 mg/m² cisplatin every three weeks concurrently with radiotherapy. The investigational arm received cisplatin (80 mg/m² d1) and fluorouracil (800 mg/m² civ d1-5) every three weeks for two cycles before CCRT. The primary endpoint was disease-free survival (DFS) and distant metastasis-free survival (DMFS). Secondary endpoint was overall survival (OS). Results: 476 patients were randomly assigned to the investigational (n = 238) and control arms (n = 238). The investigational arm achieved higher 3-year DFS rate (82.0%, 95% CI = 0.77-0.87) than the control arm (74.1%, 95% CI = 0.68-0.80, P = 0.028). The 3-year DMFS rate was 86.0% for the investigational arm versus 82.0% for the control arm, with marginal statistical significance (P = 0.056). However, there were no statistically significant differences in OS or locoregional relapse-free survival (LRRFS) rates between two arms (OS: 88.2% vs 88.5%, P = 0.815; LRRFS: 94.3% vs 90.8%, P = 0.430). The most common grade 3–4 toxicity during NACT was neutropenia (16.0%). During CCRT, the investigational arm experienced statistically significantly more grade 3–4 toxicities (P < 0.001). Conclusions: NACT improved tumor control compared with CCRT alone in locoregionally advanced NPC, particularly at distant sites. However, there was no early gain in overall survival. Longer follow-up is needed to determine the eventual therapeutic efficacy. Clinical trial information: NCT00705627.