In a Chinese phase III trial reported in The New England Journal of Medicine, Yuan Zhang, MD, PhD, and colleagues found that the addition of gemcitabine/cisplatin induction chemotherapy to standard platinum-based chemoradiotherapy improved recurrence-free survival vs chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma.
Study Details
The open-label trial included 480 patients with newly diagnosed disease from 12 centers. Patients were randomly assigned between December 2013 and September 2016 to receive gemcitabine at 1 g/m2 on days 1 and 8 and cisplatin at 80 mg/m2 on day 1 every 3 weeks for three cycles plus standard chemoradiotherapy (n = 242) or standard chemoradiotherapy alone (n = 238). Chemoradiotherapy consisted of 100 mg/m2 of cisplatin every 3 weeks on days 1, 22, and 43, plus intensity-modulated radiotherapy. Randomization was stratified by treatment center and disease stage III or IV. It was recommended that patients in the induction chemotherapy group begin chemoradiotherapy within 21 to 28 days after the first day of the last cycle of induction chemotherapy.
The primary endpoint was recurrence-free survival in the intention-to-treat population.
Recurrence-Free Survival
Median follow-up was 42.7 months. In total, 96.7% of patients in the induction chemotherapy group completed three cycles of induction chemotherapy. Recurrence-free survival at 3 years was 85.3% with induction chemotherapy vs 76.5% with standard therapy (stratified hazard ratio [HR] = 0.51, P = .001). Overall survival at 3 years was 94.6% vs 90.3% (HR = 0.43, 95% confidence interval [CI] = 0.24–0.77). The 3-year distant recurrence-free survival rates were 91.1% vs 84.4% (HR = 0.43, 95% CI = 0.25–0.73), and the 3-year locoregional recurrence-free survival rates were 91.8% vs 91.0% (HR = 0.77, 95% CI = 0.42–1.41).
Adverse Events
Acute grade 3 or 4 adverse events occurred in 75.7% of the induction-chemotherapy group and 55.7% of the standard-therapy group, with the induction-chemotherapy group having a higher incidence of neutropenia (28.0% vs 10.5%), thrombocytopenia (11.3% vs 1.3%), anemia (9.6% vs 0.8%), nausea (23.0% vs 13.9%), and vomiting (22.6% vs 13.9%). Grade 3 or 4 mucositis occurred in 28.9% vs 32.1% of patients. Grade 3 or 4 late toxicity occurred in 9.2% vs 11.4% of patients, with the most common being deafness/otitis (5.4% vs 6.8%).
The investigators concluded, “Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival as compared with chemoradiotherapy alone among patients with locoregionally advanced naso-pharyngeal carcinoma.” ■
Zhang Y, et al: N Engl J Med. September 19, 2019 (early release online).
