A phase II trial conducted in China has demonstrated that the addition of perioperative toripalimab to concurrent chemoradiotherapy significantly improves outcomes in patients with newly diagnosed, high-risk stage III to IVa locoregionally advanced nasopharyngeal carcinoma who have elevated pretreatment plasma Epstein-Barr virus (EBV) DNA concentrations. The study, led by Hai-Qiang Mai, MD, from Sun Yat-sen University Cancer Center, suggests a promising new treatment approach for this challenging cancer.
The double-blind trial, published in The Lancet Oncology, enrolled 150 patients with pretreatment plasma EBV DNA concentrations ≥ 1,500 copies/mL at Sun Yat-sen University Cancer Centre between December 2019 and December 2021. Participants were randomized in a 2:1 ratio to receive either neoadjuvant toripalimab at 240 mg (n = 100) or placebo (n = 50) every 2 weeks for two cycles. This was 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 every 3 weeks for up to eight cycles. The primary endpoint was 2-year progression-free survival.
Significant Improvement in Progression-Free Survival
After a median follow-up of 37.8 months, the 2-year progression-free survival rate was 92.0% (95% CI = 86.7%–97.3%) in the toripalimab group compared to 74.0% (95% CI = 61.8%–86.2%) in the control group. This difference was statistically significant, with a stratified hazard ratio (HR) of 0.40 (95% CI = 0.18–0.89, P = .019).
Impact on Overall Survival and Metastasis
The study also revealed improvements in other key outcomes. At 3 years, overall survival was 99.0% in the toripalimab group versus 90.0% in the control group. The cumulative incidence of distant metastasis was 9.6% versus 20.2%, and the cumulative incidence of locoregional relapse was 3.7% versus 17.0%.
Safety Profile and Adverse Events
Grade ≥ 3 adverse events occurred in 74% of patients in the toripalimab group and 68% in 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 were more frequent in the toripalimab group (42% vs 22%), with grade ≥ 3 events occurring in 10% versus 0%. Notably, no treatment-related deaths were observed in either group.
Implications and Future Directions
The investigators concluded that the “sandwich approach” involving toripalimab in the neoadjuvant and adjuvant phases, combined with concurrent chemoradiotherapy, shows promise as a therapy for locoregionally advanced nasopharyngeal carcinoma. They suggest that phase 3 non-inferiority trials are warranted to compare neoadjuvant and adjuvant toripalimab versus cisplatin plus gemcitabine neoadjuvant chemotherapy combined with concurrent chemoradiotherapy.
