Carboplatin-based versus cisplatin-based induction-concurrent chemoradiotherapy with locoregionally advanced nasopharyngeal carcinoma: A multicenter, parallel-group, non-inferiority, randomized, phase 3 trial.

6004 Background: Cisplatin-based chemoradiotherapy has been the standard of care in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). However, the cisplatin-based chemotherapy is known to the severe side-effects and poor compliance. Carboplatin is the second-generation platinum drug with similar anti-cancer efficacy but less side-effects. The purpose of this study is to investigate whether the carboplatin-based induction-concurrent chemoradiotherapy was non-inferior to the cisplatin-based induction-concurrent chemoradiotherapy in LA-NPC. Methods: We performed a multicentre, parallel-group, non-inferiority, randomized, phase 3 trial at six institutions in China. Patients initially diagonosed with non-keratinizing NPC and stage III-IVa were randomly assigned to carboplatin group or cisplatin group. Patients in the carboplatin or cisplatin group received two cycles carboplatin-based or cisplatin-based induction chemotherapy, followed by concurrent chemoradiotherapy with carboplatin or cisplatin for two or three cycles. Allocation was done by a central randomization system using sequentially numbered, opaque, sealed envelopes. The primary endpoint was 3-year failure-free survival (FFS). Secondary endpoints are overall survival (OS), distant metastasis-free survival (DMFS), loco-regional failure-free survival (LRFFS), and toxic effects. If the upper limit of the 95% CI for the difference in 3-year failure-free survival between the carboplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. This trial is registered with ClinicalTrials.gov, NCT03919552. Results: From Apr 16, 2018 to Aug 7, 2024, a total of 482 patients were enrolled and randomly assigned to carboplatin group (n=241) or cisplatin group (n=241). With a median follow-up of 40.0 months (IQR 21.0-57.0), the 3-year FFS was 85.7% (95%CI 80.4-91.0) in carboplatin group and 87.6% (83.1-92.1) in the cisplatin group (stratified hazard ratio [HR]1.234, 95% CI: 0.744-2.045, p=0.414), with a difference of 1.9% (95% CI –8.9 to 5.1; p non-inferiority=0.0112). Patients in the cisplatin group had a higher frequency of grade 3 or 4 neutropenia (31.6% vs 22.5%, p < 0.001), and anorexia (16.9% vs 3.6%, p < 0.001). A significantly higher frequency of any grade nausea (4.8% vs 3.6%, p < 0.001), vomiting (2.6% vs 0.5%, p < 0.001), and nephrotoxicity (1.3% vs 0%, p < 0.001). No patients died from treatment-related causes. Conclusions: The primary results indicated that carboplatin-based induction-concurrent chemoradiotherapy represents an alternative doublet treatment strategy to cisplatin-based induction-concurrent chemoradiotherapy for patients with LA-NPC. A longer follow-up is needed to confirm the promising regimen. Clinical trial information: NCT03919552 .