Nab-paclitaxel, cisplatin, and capecitabine versus cisplatin and gemcitabine as first line chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma: randomised phase 3 clinical trial.

OBJECTIVE

To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma.

DESIGN

Phase 3, open label, multicentre, randomised trial.

SETTING

Four hospitals located in China between September 2019 and August 2022.

PARTICIPANTS

Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma.

INTERVENTIONS

Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m on day 1), cisplatin (60 mg/m on day 1), and capecitabine (1000 mg/m twice on days 1-14) or gemcitabine (1 g/m on days 1 and 8) and cisplatin (80 mg/m on day 1).

MAIN OUTCOME MEASURES

Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population.

RESULTS

The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) 13/40 (33%); P=0.02), neutropenia (6/41 (15%) 16/40 (40%); P=0.01), and anaemia (1/41 (2%) 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up.

CONCLUSION

The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival.

TRIAL REGISTRATION

Chinese Clinical Trial Registry ChiCTR1900027112.