In a Chinese phase II trial reported in the Journal of Clinical Oncology, Li et al found that treatment with two cycles of concurrent cisplatin and intensity-modulated radiotherapy (IMRT) was noninferior to three cycles in progression-free survival and associated with reduced toxicity in patients with Epstein-Barr virus (EBV) DNA–selected low-risk locoregionally advanced nasopharyngeal carcinoma.
Study Details
In the open-label multicenter trial, 332 patients with pretreatment EBV DNA levels < 4,000 copies/mL were randomly assigned between September 2016 and October 2018 to receive two cycles of concurrent cisplatin (100 mg/m2 on days 1 and 22) and IMRT (n = 166) or three cycles (cisplatin on days 1, 22, and 43) of concurrent chemoradiation (n = 166). The prescribed radiotherapy doses for planning target volumes ranged from 68–70 Gy to 50–54 Gy in 30 to 33 fractions daily at 5 fractions per week over 6 to 7 weeks. The primary endpoint was 3-year progression-free survival.
Progression-Free Survival
Median follow-up was 37.7 months (interquartile range = 33.0–46.1 months). Estimated 3-year progression-free survival rates were 88.0% (95% confidence interval [CI] = 83.1%–92.9%) in the two-cycle group vs 90.4% (95% CI = 85.7%–95.1%) in the three-cycle group (difference = 2.4%, 95% CI = –4.3% to 9.1%, P = .014 for noninferiority).
No significant differences between the two-cycle group vs three-cycle group were observed in progression-free survival (hazard ratio [HR] = 1.20, 95% CI = 0.63–2.29, P = .59), overall survival (HR = 1.00, 95% CI = 0.20–4.94, P = 1.00), cumulative incidence of locoregional relapse (HR = 1.15, 95% CI = 0.42–3.15, P = .79), or cumulative incidence of distant metastasis (HR = 1.22, 95% CI = 0.53–2.82, P = .64).
Adverse Events
Grade 3 or 4 acute toxicities occurred in 74.7% of the two-cycle group vs 80.0% of the three-cycle group, with mucositis (24.8% vs 15.1%), hyponatremia (15.8% vs 8.4%), and dermatitis (5.5% vs 1.2%) being significantly more common in the three-cycle group. Any-grade dry mouth, dysphagia, weight loss, and fatigue were more common in the three-cycle group. The overall any-grade toxicity burden (T score = 12.33 vs 10.57, P < .001) and grade 3 or 4 toxicity burden (T score = 1.76 vs 1.44, P = .05) were greater in the three-cycle group. Among late toxicities, the three-cycle group had increased rates of any-grade hearing impairment (35.2% vs 22.9%), dry mouth (78.8% vs 63.9%), and skin fibrosis (29.7% vs 18.7%), with rates of grade 3 or 4 events being similar in the two groups. No treatment-related deaths were observed.
KEY POINTS
- Two cycles of concurrent chemoradiation was noninferior to three cycles in 3-year progression-free survival.
- Toxicity burden was greater with three cycles.
The investigators concluded: “Intensity-modulated radiotherapy plus two cycles of concurrent [cisplatin at] 100 mg/m2 could be an alternative treatment option for patients with low-risk [locally advanced nasopharyngeal carcinoma].”
Hai-Qiang Mai, MD, PhD, Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Key R&D Program of China, National Natural Science Foundation of China, and others. For full disclosures of the study authors, visit ascopubs.org.
