847O - Sequential chemoradiotherapy versus induction chemotherapy plus concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: A multicentre, open-label, non-inferiority, randomised, phase III trial

Background

Given that intensity-modulated radiation therapy (IMRT) improves local control and that chemotherapy administered either before or after radiotherapy reduces the risk of distant failure, it is imperative to investigate whether a sequential chemoradiotherapy (SCRT) regimen could serve as an alternative to the induction chemotherapy + concurrent chemoradiotherapy (IC+CCRT) protocol for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients.

Methods

This open-label, phase III, non-inferiority clinical trial was conducted at six centers in China from January 2018 to September 2021. Patients aged 18–65 years diagnosed with stage T1-4N2-3 or T3-4N0-1 M0 NPC were randomly assigned (1:1) to receive either (1) two cycles of IC with GP regimen (gemcitabine 1000mg/m² d1,8 + cisplatin 25 mg/m² d1–3, q21d) followed by IMRT, and then two cycles of adjuvant chemotherapy (AC) with the same regimen, or (2) two cycles of IC with GP regimen followed by IMRT plus concomitant weekly cisplatin (30 mg/m²). The primary endpoint of the study was the 3-year failure-free survival (FFS) rate with non-inferiority margin of 10% (HR < 1.6).

Results

A total of 420 patients were randomly assigned to SCRT or IC+CCRT group (n = 210 each). After a median follow-up of 47.0 months (IQR: 35.0-57.8), the 3-year FFS rate was 84.0% in the SCRT group compared to 79.8% in the IC+CCRT group (log-rank P = 0.344), with a HR of 0.804 (95% CI, 0.510-1.266) and an absolute difference of 4.2% (95% CI, -3.2 to 11.6). No significant differences were observed between the groups in 3-year overall survival, locoregional control, or distant metastasis-free survival. Compared to the IC+CCRT group, the SCRT group experienced significantly lower incidences of grade ≥3 acute nonhematological adverse events (AEs) due to the omission of concurrent chemotherapy. This included reductions in acute mucositis (29.0% vs. 41.9%, P < 0.001), nausea (9.5% vs. 18.1%, P = 0.011), and vomiting (3.8% vs. 9.5%, P = 0.019).

Conclusions

For patients with LA-NPC, SCRT demonstrated non-inferiority in terms of 3-year FFS compared to IC+CCRT with fewer sever nonhematological AEs during IMRT.

Clinical trial identification

NCT03366415.

Editorial acknowledgement

Funding

Shanghai Sailing Program (No. 21YF1408400), Scientific and Innovative Action Plan of Shanghai (No. 21Y11911900).

Disclosure

All authors have declared no conflicts of interest.