Final survival analysis of induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by concurrent chemoradiotherapy in nasopharyngeal carcinoma: a multicenter, randomized, phase 3 trial.

In nasopharyngeal carcinoma, cisplatin is known to be associated with poor treatment compliance and notable side effects. More effective and safer platinum drugs are needed for the treatment of patients with nasopharyngeal carcinoma. In 2021, our multicenter, randomized, phase 3 trial reported that lobaplatin and fluorouracil induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than did cisplatin-based therapy in nasopharyngeal carcinoma. Data from the 10-year survival analysis are updated here. With a median follow-up of 10.6 years in the intention-to-treat population, 10-year progression-free survival is 70.7% in the lobaplatin-based therapy group vs. 71.9% in the cisplatin-based therapy group (HR 1.02, 95% CI 0.72-1.43; log-rank p = 0.885). The difference between the groups is 1.2% (95% CI -6.7-9.1, pnon-inferiority = 0.015), which is lower than the prespecified non-inferiority margin of 10%. The results are similar when we analyze patients in the per-protocol population. In the univariable and multivariable analyses, stage is an independent prognostic factor for progression-free survival (p = 0.001). The subgroup analyses suggest that the non-inferiority of lobaplatin-based therapy did not differ among specific populations. The incidence of late toxic effects is similar between the therapy groups, except for grades 1-2 peripheral neuropathy (p = 0.033), grades 1-2 deafness/otitis (p = 0.021), and grades 1-2/3 nephrotoxicity (p = 0.005; p = 0.021), the incidence of which is greater in the cisplatin-based therapy group than in the lobaplatin-based therapy group. Our findings suggest that lobaplatin and fluorouracil induction chemotherapy plus lobaplatin-based concurrent chemoradiotherapy is an alternative doublet treatment strategy to cisplatin-based concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma.