Induction chemotherapy with nab-paclitaxel and cisplatin versus docetaxel, cisplatin, and fluorouracil followed by chemoradiotherapy in patients with stage III–IVA nasopharyngeal carcinoma: An open-label, noninferiority, randomized, controlled, phase

6013 Background: The docetaxel, cisplatin, and 5-fluorouracil (TPF) regimen is the standard induction therapy regimen for locoregionally advanced nasopharyngeal carcinoma (LANPC). However, it is associated with poor patient compliance and notable side effects. This phase 3 trial aimed to compare the efficacy and safety of induction chemotherapy with nab-paclitaxel plus cisplatin (nab-TP) with those of the TPF regimen in patients with LANPC. Methods: In this multicenter, noninferiority, open-label, randomized controlled trial, treatment-naive patients with LANPC were recruited from 5 hospitals in China and were randomly assigned to receive two cycles of nab-TP (nab-paclitaxel 260 mg/m², cisplatin 80 mg/m²) or TPF (docetaxel 60 mg/m², cisplatin 60 mg/m², 5-FU 3 g/m²), followed by concurrent chemoradiotherapy. The primary endpoint was the 3-year failure-free survival (FFS) rate (non-inferiority margin 10%) in the intention-to-treat population. Secondary endpoints included overall survival, treatment response, safety, and patient-reported outcomes. This trial is registered with chictr.org.cn (ChiCTR1800019922) and is now completed. Based on previous studies, we hypothesized that the 3-year FFS (approximately 80%) is the same between the TPF regimen and the nab-TP regimen for patients with LANPC. We specify a clinically acceptable noninferiority margin of 10%. The dropout rate in both arms was set at 4% per year. Accordingly, a minimum of 506 participants was needed to achieve 80% statistical power with a one-sided type I error of 2·5%. Results: Between January 22, 2019 and March 24, 2023, 515 patients (71·8% male; median age: 45 years (IQR 37–51)) were randomized: 259 to the nab-TP group and 256 to the TPF group. Compared with the TPF group, the nab-TP group had significantly better treatment compliance. With a median follow-up of 55·2 months, the 3-year FFS rate in the intention-to-treat population was 86·7% (95% confidence interval (CI): 82·6–90·9) in the nab-TP group and 88·2% (95% CI: 84·2–92·1) in the TPF group. The difference in the 3-year FFS between groups was -1·4% (95% CI: -7·2 to 4·3)(P non-inferiority = 0·0018). Compared with the TPF group, the nab-TP group had significantly lower incidences of grade 1+ leucopenia (34·0% vs. 62·6%, P < 0·0001), neutropenia (20·3% vs. 48·8%, P < 0·0001), electrolyte disturbances (86·3% vs. 96·5%, P < 0·0001), and diarrhea (28·5% vs. 39·0%, P = 0·012), whereas the nab-TP group had a higher incidence of nausea (91·0% vs. 85·4%, P =0·047). No treatment-related death was documented. Conclusions: In LANPC, nab-TP was non-inferior to TPF in terms of 3-year FFS rate and was associated with a significantly better safety and tolerability profile, supporting its use as a viable therapeutic alternative. Clinical trial information: ChiCTR1800019922.