Carboplatin Matches Cisplatin Efficacy With Reduced Toxicity in LA-NPC Chemoradiotherapy

Carboplatin-based induction-concurrent chemoradiotherapy (IC-CCRT) demonstrated noninferior efficacy compared with cisplatin-based IC-CCRT while producing fewer high-grade toxicities in patients with locally advanced nasopharyngeal carcinoma (LA-NPC), according to results from a multicenter, randomized, phase 3 trial (NCT03919552) presented at the 2026 ASCO Annual Meeting.

In the intent-to-treat (ITT) population, the primary end point of 3-year failure-free survival (FFS) was 84.8% (95% CI, 79.5%-90.1%) with carboplatin-based IC-CCRT vs 86.8% (95% CI, 82.1%-91.5%) with cisplatin-based IC-CCRT (HR, 1.15; 95% CI, 0.70-1.87; P = .584), meeting the noninferiority threshold. FFS events occurred in 12.4% vs 14.5% of patients in the respective arms. Results in the per-protocol population were consistent, with 3-year FFS of 84.7% vs 86.1% (HR, 1.10; 95% CI, 0.65-1.88; P = .656). Subgroup analyses across the ITT population revealed no significant differences in FFS between key patient subgroups.

Secondary end points including overall survival (OS), distant metastasis-free survival (DMFS), and locoregional FFS (LRFFS) followed similar patterns. Three-year OS was 96.2% (95% CI, 93.5%-98.9%) with carboplatin vs 97.4% (95% CI, 95.0%-99.8%) with cisplatin (HR, 0.85; 95% CI, 0.33-2.21; P = .745). Three-year DMFS was 91.0% (95% CI, 86.7%-95.3%) vs 89.6% (95% CI, 85.5%-93.7%), respectively (HR, 1.59; 95% CI, 0.87-2.92; P = .130), and 3-year LRFFS was 91.6% (95% CI, 87.3%-95.9%) vs 95.3% (95% CI, 92.4%-98.2%; HR, 0.83; 95% CI, 0.41-1.70; P = .613).

"In the ITT population and the [per-protocol] population, carboplatin-based IC-CCRT was non-inferior to cisplatin-based IC-CCRT in LA-NPC, and was associated with a lower toxicity profile," said principal investigator Jian Guan, MD, oncologist at Nanfang Hospital and Southern Medical University in Guangzhou, China. "These findings support carboplatin-based IC-CCRT as a promising alternative treatment option for LA-NPC."

Safety

The carboplatin regimen produced a lower overall incidence of grade 3 or higher toxicities compared with cisplatin (51% vs 62%). Specific reductions were observed in neutropenia (23% vs 31%), anemia (4% vs 17%), nausea (8% vs 11%), and vomiting (1% vs 7%). Any-grade nephrotoxicity also occurred less frequently with carboplatin (18% vs 43%). The notable exception was thrombocytopenia, which was more common with carboplatin at any grade (39% vs 21%).

Study Design

The phase 3 trial enrolled patients aged 18 to 65 years with newly diagnosed, histologically confirmed NPC, stage III to IVa disease per American Joint Committee on Cancer 8th edition criteria, a Karnofsky performance score greater than 70, and adequate organ function. A total of 482 patients were randomized 1:1 to carboplatin area under the curve (AUC) 4 or cisplatin 75 mg/m² plus docetaxel 75 mg/m² every 3 weeks for 2 induction cycles. Concurrent chemoradiotherapy consisted of carboplatin AUC 5 or cisplatin 100 mg/m² with intensity-modulated radiotherapy every 3 weeks for 2 or 3 cycles.

Median age was 49 years (IQR, 39-54) in the carboplatin arm and 48 years (IQR, 39-53) in the cisplatin arm; 73% and 75% of patients were male, respectively. Most patients had a Karnofsky performance score of 90 (69% vs 75%), WHO-III pathology (95% in each arm), and pretreatment Epstein-Barr virus DNA up to 2000 copies/mL (64% vs 67%). T3 disease was present in 57% vs 62% of patients, N3 disease in 40% vs 42%, and stage IVa disease in 54% of each arm. The primary end point was 3-year FFS; secondary end points included OS, LRFFS, DMFS, response rates, and toxicities.

Reference

1. Wang XQ, Chen M, Liu X, et al. Carboplatin-based versus cisplatin-based induction-concurrent chemoradiotherapy with locoregionally advanced nasopharyngeal carcinoma: a multicenter, parallel-group, non-inferiority, randomized, phase 3 trial. J Clin Oncol. 2026;44(suppl 15):6004. doi:10.1200/JCO.2026.44.16_suppl.6004