Randomized, multicenter phase 3 study evaluating radiotherapy versus concurrent chemoradiotherapy in nasopharyngeal carcinoma patients achieving CR/PR after induction chemotherapy.

BACKGROUND

The present study sought to compare the clinical efficacy and safety profiles of radiotherapy (RT) and concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients who attained complete or partial response (CR/PR) following induction chemotherapy (IC).

METHODS

This multicenter, randomized, open-label, phase 3 noninferiority trial was conducted at 7 Chinese hospitals. Patients with newly diagnosed stage III-IVb NPC who achieved CR/PR after IC were randomly allocated (1:1) to either the RT (IC + RT) group or the CCRT (IC + CCRT) group. The chemotherapy protocol was identical across the two treatment groups. The primary endpoint was progression-free survival (PFS). Secondary endpoints comprised overall survival (OS) and the incidence of adverse events. Statistical analyses were performed using the Kaplan-Meier method and log-rank test.

RESULTS

From December 2016 to May 2023, 220 eligible patients with histologically confirmed nasopharyngeal carcinoma were enrolled. The trial was terminated early due to slow accrual. Of these patients, 109 were assigned to the IC + RT group and 111 to the IC + CCRT group. The median follow-up was 57 months (range, 8-107 months). The IC + RT and IC + CCRT groups showed comparable 5-year progression-free survival rates (87.0% vs. 80.7%, P = 0.21). No significant differences were observed between the two treatment arms with respect to local relapse-free survival, regional relapse-free survival, locoregional relapse-free survival, distant metastasis-free survival, or overall survival (all P > 0.05). The IC + RT group had significantly lower incidences of grade 3-4 hematologic and gastrointestinal toxicities than the IC + CCRT group. Additionally, grade 1-2 deafness/otitis and liver dysfunction were also less frequent in the IC + RT group.

CONCLUSIONS

In NPC patients achieving CR/PR after induction chemotherapy, IC + RT demonstrated a favorable safety profile compared with IC+CCRT. Although the observed survival outcomes were numerically comparable, the premature termination of the trial and insufficient statistical power preclude a definitive noninferiority claim. These hypothesis-generating findings warrant validation in future adequately powered trials.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT03015727.