In a Chinese single-center phase II trial reported in The Lancet Oncology, Lin et al found that the addition of perioperative toripalimab to concurrent chemoradiotherapy was active in patients with newly diagnosed high-risk stage III to IVa locoregionally advanced nasopharyngeal carcinoma with elevated pretreatment plasma Epstein-Barr virus (EBV) DNA concentrations.
Study Details
In the double-blind trial, 150 patients with pretreatment plasma EBV DNA concentration ≥ 1,500 copies/mL were enrolled at Sun Yat-sen University Cancer Centre between December 2019 and December 2021. Patients were randomly assigned 2:1 to receive neoadjuvant toripalimab at 240 mg (n = 100) or placebo (n = 50) once every 2 weeks for two cycles, followed by neoadjuvant concurrent cisplatin at 100 mg/m2 on days 1, 22, and 43 during intensity-modulated radiotherapy (54–70 Gy in 33 fractions) and adjuvant toripalimab at 240 mg or placebo once every 3 weeks for up to eight cycles. The primary endpoint was 2-year progression-free survival.
Key Findings
Median follow-up for progression-free survival was 37.8 months. Progression-free survival at 2 years was 92.0% (95% CI = 86.7%–97.3%) in the toripalimab group vs 74.0% (95% CI = 61.8%–86.2%) in the control group (stratified hazard ratio [HR] = 0.40, 95% CI = 0.18–0.89, P = .019).
At 3 years, overall survival was 99.0% vs 90.0%, cumulative incidence of distant metastasis was 9.6% vs 20.2%, and cumulative incidence of locoregional relapse was 3.7% vs 17.0%.
Grade ≥ 3 adverse events occurred in 74% of the toripalimab group and 68% of the control group; the most common events in both groups were leukopenia (40% vs 44%), mucositis (28% vs 20%), and neutropenia (17% vs 18%). Immune-mediated adverse events of any grade occurred in 42% vs 22%, with grade ≥ 3 events in 10% vs 0%. No treatment-related deaths were observed.
The investigators concluded: “Our findings suggested that a so-called sandwich approach involving toripalimab (in the neoadjuvant and adjuvant phases) combined with concurrent chemoradiotherapy could be a highly promising therapy for the treatment of locoregionally advanced nasopharyngeal carcinoma. Phase 3 non-inferiority trials are warranted comparing neoadjuvant and adjuvant toripalimab versus cisplatin plus gemcitabine neoadjuvant chemotherapy combined with concurrent chemoradiotherapy.”
Hai-Qiang Mai, MD, Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 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.
