Effect of Concurrent Chemoradiotherapy With Nedaplatin vs Cisplatin on the Long-term Outcomes of Survival and Toxic Effects Among Patients With Stage II to IVB Nasopharyngeal Carcinoma: A 5-Year Follow-up Secondary Analysis of a Randomized Clinical Trial

Abstract

Importance: Nedaplatin-based concurrent chemoradiotherapy (CCRT) regimen at 2 years was noninferior to cisplatin-based regimen in patients with locoregional, stage II to IVB nasopharyngeal carcinoma (NPC) and was associated with fewer late adverse events, but longer-term outcomes and toxicity are unclear.

Objective: To evaluate the 5-year outcomes and late toxicity profile of nedaplatin-based CCRT in patients with locoregional, stage II to IVB NPC.

Design, settings, and participants: This 5-year follow-up secondary analysis of an open-label, noninferiority, multicenter randomized clinical trial enrolled patients with nonkeratinizing stage II to IVB NPC between January 16, 2012, and July 16, 2014, with a median follow-up duration of 78 months (IQR, 3-99 months). Data analysis was conducted from November 10, 2020, to July 8, 2021.

Interventions: Patients were randomly assigned (1:1) to receive nedaplatin (100 mg/m2)- or cisplatin (100 mg/m2)-based chemotherapy every 3 weeks for 3 cycles concurrently with intensity-modulated radiotherapy.

Main outcomes and measures: The primary end point was progression-free survival (PFS). Secondary end points were overall survival, distant metastasis-free survival, and locoregional relapse-free survival.

Results: A total of 402 eligible participants were enrolled (median [IQR] age, 45 [18-65] years; 302 [75.1%] male). Patients were randomly assigned to receive nedaplatin- or cisplatin-based CCRT (n = 201 for each): 196 patients (97.5%) started nedaplatin-based CCRT and 197 patients (98.0%) started cisplatin-based CCRT. Intention-to-treat analysis demonstrated a 5-year progression-free survival rate of 81.4% (95% CI, 75.9%-86.9%) for the cisplatin group and 79.8% (95% CI, 74.1%-85.5%) for nedaplatin group, with a difference of 1.6% (95% CI, -6.3% to 9.5%; P = .002 for noninferiority). No significant survival differences were observed between the cisplatin and nedaplatin groups for 5-year overall survival (89.4% vs 88.8%, P = .63), distant metastasis-free survival (85.9% vs 90.4%, P = .17), and locoregional relapse-free survival (92.6% vs 89.6%, P = .17) rates. The cisplatin group had a higher incidence of grade 3 and 4 auditory toxic effects than the nedaplatin group (35 [17.7%] vs 21 [10.5%], P = .04).

Conclusions and relevance: In this secondary analysis of a randomized clinical trial, long-term analysis confirmed that nedaplatin-based CCRT could be regarded as an alternative doublet treatment strategy to cisplatin-based CCRT in stage II to IVB NPC.

Trial registration: ClinicalTrials.gov Identifier: NCT01540136.

Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure 1.. Flowchart of Patients Included and Excluded in This Study

CCRT indicates concurrent chemoradiotherapy.

Figure 2.. Progression-Free and Overall Survival and Cumulative Incidence of Distant Metastasis and Locoregional Relapse in the Intention-to-Treat Population

HR indicates hazard ratio.

Figure 3.. Treatment Effects on Survival Within Subgroups

The number of events and the number of patients are shown by study arm. Hazard ratios (HRs) and 95% CIs were calculated in a univariate Cox proportional hazards regression model; interaction and stratified analyses were conducted according to sex, age, Karnofsky score, and stage.