Nab-paclitaxel plus cisplatin versus docetaxel plus cisplatin and 5-FU induction chemotherapy followed by concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma: A multicenter parallel controlled phase III trial.

Abstract

6071 Background: Although several large phase III clinical trials and meta-analysis have demonstrated significant clinical benefit of docetaxel combined with cisplatin and 5-FU (TPF) chemotherapy in head and neck cancer, serious adverse reactions are unsatisfactory. Therefore, this study was designed to evaluate the efficacy and safety of nab-paclitaxel plus cisplatin (TP) versus TPF induction chemotherapy (ICT) followed by concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal carcinoma (LA-NPC). Methods: In this open-label, phase 3 trial, patients were randomized 1:1 to received TP (260 mg/m2 nab-paclitaxel and 80 mg/m2 cisplatin on days 1 and 22) or TPF (60 mg/m2 docetaxel and 60 mg/m2 cisplatin on days 1 and 22; 3 g/m2 5-Fu on days 1-5 and 22-26) every 3 weeks for 2 cycles, both groups of patients received CCRT (100mg/m2 cisplatin and IMRT on days 43 and 64) every 21 days for 2 cycles. The primary endpoint was failure-free survival. Secondary endpoints included overall survival, objective response rate (ORR), quality of life and safety. Results: From January 2019 to July 2021, 281 patients were randomized to TP (n = 142, TP arm) or TPF (n = 139, TPF arm). The median age was 44 years (range, 20-63) in the TP arm and 45 years (range, 18-69) in the TPF arm. The pathological stages were 40.85% stage III and 59.15% stage IVA in the TP arm, while those of the TPF arm were 43.17% stage III and 56.83% stage IVA. There were 99.30% and 97.12% undifferentiated nonkeratinizing carcinoma in the two groups, respectively. All patients had Karnofsky performance status of 90. ICT was completed in 98.93% (100% in the TP arm and 97.84% in the TPF arm). The median relative dose intensity of nab-paclitaxel and cisplatin were 99.96% and 99.81% in the TP arm, 99.83%, 100% and 100% for docetaxel, cisplatin and 5-FU in the TPF arm, respectively. The ORR were 80.28% in the TP arm and 78.26% in the TPF arm after two cycles of ICT. 85.77% (83.10% in the TP arm and 88.49% in the TPF arm) completed the CCRT. After two cycles of CCRT, the ORR were 99.25% and 99.24%, respectively. 3 months after completion of all treatment, the ORR were 99.25% and 99.25%, respectively. During ICT, all treatment-related adverse events occurred in 40.14% of patients in the TP arm and 57.55% in the TPF arm. The most frequent grade 3 adverse events were neutropenia (0.70% vs 2.16%), leucopenia (0 vs 2.88%), diarrhea (0 vs 0.72%) in the TP arm and in the TPF arm. Over the entire course of treatment, the most common was 1 grade adverse events, and no patient developed grade 4 adverse events in the two groups. Conclusions: In this study, TP regimen showed similar trends in the ORR but excellent safety profile in patients with LA-NPC compared with TPF regimen, suggesting a potential therapeutic option for this population. Clinical trial information: ChiCTR1800019922 .