In a Chinese phase III trial reported in The Lancet Oncology, Liu et al found that adjuvant cisplatin/gemcitabine improved progression-free survival vs cisplatin/fluorouracil following chemoradiotherapy in previously untreated patients with N2 or N3 nasopharyngeal carcinoma.
Study Details
In the open-label trial, 240 patients from four Chinese centers were randomly assigned between October 2017 and July 2020 to receive adjuvant cisplatin/gemcitabine (n = 120) or cisplatin/fluorouracil (n = 120) following concurrent chemoradiotherapy with cisplatin given at 100 mg/m² on days 1, 22, and 43 of intensity-modulated radiotherapy (54–70 Gy in 33 fractions, with 5 daily fractions per week for 7 weeks).
Adjuvant chemotherapy consisted of three cycles of either:
- Gemcitabine at 1 g/m² on days 1 and 8 and cisplatin at 80 mg/m² on day 1 every 3 weeks
- Fluorouracil at 4 g/m² via continuous infusion for 96 hours and cisplatin at 80 mg/m² on day 1 every 4 weeks.
The primary endpoint was 3-year progression-free survival in the intention-to-treat population.
Progression-Free Survival
At data cutoff (December 2022), median follow-up was 40 months (interquartile range = 32–48 months). Progression-free survival at 3 years was 83.9% (95% confidence interval [CI] = 75.9%–89.4%) in the cisplatin/gemcitabine group vs 71.5% (95% CI = 62.5%–78.7%) in the cisplatin/fluorouracil group (stratified hazard ratio [HR] = 0.54, 95% CI = 0.32–0.93, P = .023).
Three-year rates were:
- 7% (95% CI = 83.8%–94.7%) in the cisplatin/gemcitabine group vs 94.0% (95% CI = 87.8%–97.1%) for overall survival (stratified HR = 1.17, 95% CI = 0.51–2.66, P = .71)
- 6% (95% CI = 0.8%–8.1%) vs 13.2% (95% CI = 7.8%–22.4%) for locoregional relapse (stratified HR = 0.33, 95% CI = 0.12–0.90, P = .030)
- 9% (95% CI = 6.2%–19.2%) vs 22.3% (95% CI = 14.9%–33.2%) for distant metastases (stratified HR = 0.50, 95% CI = 0.26–0.98, P = .042).
Adverse Events
Grade 3 or 4 adverse events occurred in 83% of patients in the cisplatin/gemcitabine group vs 68% of the gemcitabine/fluorouracil group; the most common in the cisplatin/gemcitabine group were leukopenia (52% vs 29%, P = .00039), neutropenia (32% vs 16%, P = .010), and mucositis (23% vs 28%, P = .43). The most common adverse events leading to discontinuation of treatment were leukopenia (7%) and thrombocytopenia (3%) in the cisplatin/gemcitabine group, and leukopenia (3%) and anemia (2%) in the cisplatin/fluorouracil group. The most common grade ≥ 3 late adverse event (≥ 3 months after completion of radiotherapy) was auditory or hearing loss (5% vs 9%). One treatment-related death occurred in the cisplatin/gemcitabine group due to septic shock.
The investigators concluded, “Our findings suggest that concurrent adjuvant cisplatin/gemcitabine could be used as an adjuvant therapy in the treatment of patients with N2 [or N]3 nasopharyngeal carcinoma, although long-term follow-up is required to confirm the optimal therapeutic ratio.”
Hai-Qiang Mai, MD, of the Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Centre, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the National Key Research and Development Program of China, National Natural Science Foundation of China, and others. For full disclosures of the study authors, visit thelancet.com.
