Carboplatin-Based IC-CCRT Better Tolerated Vs Cisplatin in LA-NPC

Receipt of carboplatin-based induction-concurrent chemoradiotherapy (IC-CCRT) displayed noninferior efficacy and a lower frequency of toxicities vs cisplatin-based IC-CCRT among patients with locally advanced nasopharyngeal carcinoma (LA-NPC), according to findings from a multicenter, parallel-group phase 3 trial (NCT03919552) presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.

Efficacy Data

Regarding the primary end point of failure-free survival (FFS) in the intent-to-treat (ITT) population, noninferior outcomes were observed between patients who received carboplatin (n = 241) vs cisplatin (n = 241), with an HR of 1.15 (95% CI, 0.70-1.87; P = .584). FFS events were observed in 12.4% vs 14.5% of the respective arms, and the 3-year FFS rates were 84.8% (95% CI, 79.5%-90.1%) vs 86.8% (95% CI, 82.1%-91.5%). In the per-protocol populations for carboplatin (n = 191) and cisplatin (n = 186), a similar trend was observed; the 3-year FFS rate was 84.7% (95% CI, 79.0%-90.4%) vs 86.1% (95% CI, 81.0%-91.2%), respectively (HR, 1.10; 95% CI, 0.65-1.88; P = .656).

Moreover, in a subgroup analysis of FFS across the ITT population, no significant differences were observed between key subgroups.

Regarding secondary end points, including overall survival (OS), distant metastasis-free survival (DMFS), and locoregional FFS (LRFFS), similar non-inferiority outcomes were observed. The 3-year OS rates between the carboplatin and cisplatin arms were 96.2% (95% CI, 93.5%-98.9%) vs 97.4% (95% CI, 95.0%-99.8%), respectively (HR, 0.85; 95% CI, 0.33-2.21; P = .745). The 3-year DMFS rates were 91.0% (95% CI, 86.7%-95.3%) vs 89.6% (95% CI, 85.5%-93.7%) in each arm (HR, 1.59; 95% CI, 0.87-2.92; P = .130); the 3-year LRFFS rates were 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,” Jian Guan, MD, oncologist at Nanfang Hospital and Southern Medical University in Guangzhou, China, and principal investigator of the phase 3 study, stated in the presentation.“These findings support carboplatin-based IC-CCRT as a promising alternative treatment option for LA-NPC.”

Phase 3 Trial Design and Population

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

In the carboplatin and cisplatin arms, the median age was 49 years (IQR, 39-54) vs 48 years (IQR, 39-53), and 73% vs 75% of each arm were male. Most patients in each arm had a KPS of 90 (69% vs 75%), WHO-III pathology (95% vs 95%), and received up to 2000 copy/mL of pretreatment with an Epstein-Barr virus DNA test (64% vs 67%). Additionally, 57% vs 62% of patients had T3 disease, 40% vs 42% had N3 disease, and 54% in each cohort had stage IVa disease.

The primary end point of the trial was 3-year FFS. Secondary end points included OS, LRFFS, DMFS, response rates, and toxicities.

Safety Outcomes

Regarding safety outcomes, the carboplatin-based regimen exhibited a lower frequency of grade 3 or higher toxicities vs the cisplatin group, including neutropenia (23% vs 31%), anemia (4% vs 17%), nausea (8% vs 11%), and vomiting (1% vs 7%); the overall incidence of grade 3 or higher toxicities was 51% vs 62% in each arm. Additionally, the rate of any-grade nephrotoxicity was lower with carboplatin (18% vs 43%). However, a greater proportion of patients experienced any-grade thrombocytopenia compared with cisplatin-based IC-CCRT (39% vs 21%).

Reference

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