In a Chinese single-center phase II trial (EC-CRT-001) reported in The Lancet Oncology, Zhu et al found that the addition of the PD-1 inhibitor toripalimab to definitive chemoradiotherapy resulted in “encouraging activity and acceptable toxicity” in patients with locally advanced esophageal squamous cell carcinoma. As noted by the investigators, toripalimab is approved in China for the treatment of advanced esophageal squamous cell carcinoma, but its efficacy in locally advanced disease is unclear.
Study Details
In the trial, 42 patients with untreated, unresectable, stage I to IVA disease were enrolled at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Patients received concurrent thoracic radiotherapy at 50.4 Gy in 28 fractions, chemotherapy with five cycles of weekly paclitaxel at 50 mg/m² and cisplatin at 25 mg/m², and toripalimab at 240 mg every 3 weeks for up to 1 year or until disease progression or unacceptable toxicity. Overall, 93% of patients had stage III or IVA disease. The primary endpoint was investigator-assessed complete response rate at 3 months after radiotherapy.
KEY POINTS
- The addition of toripalimab to definitive chemoradiotherapy produced a complete response in 62% of patients at 3 months after radiotherapy.
- Among all responders, median duration of response was 12.1 months.
Responses
Planned chemoradiotherapy was completed by 40 (95%) of 42 patients. At 3 months after radiotherapy, a complete response was observed in 26 (62%, 95% confidence interval [CI] = 46%–76%) of 42 patients. Partial response was observed in nine patients (21%), and stable disease was seen in two (5%). Best response after radiotherapy was complete in 26 patients (62%), partial in 15 (36%), and stable disease in 1 (2%). Among all responders, the median duration of response was 12.1 months (95% CI = 5.9–18.2 months). A complete response was observed in 8 (73%) of 11 patients with a PD-L1 combined positive score (CPS) ≥ 10 vs 16 (55%) of 29 with a CPS < 10 (P = .52).
After a median follow-up of 14.9 months (interquartile range = 11.9–18.4 months), median overall survival was not reached, and 1-year overall survival was 78.4% (95% CI = 66.9%–92.0%). Median progression-free survival was 12.2 months (95% CI = 9.1–15.3 months) and 1-year progression-free survival was 54.5% (95% CI = 41.3%–72.0%).
Adverse Events
Treatment-related grade ≥3 adverse events occurred in 86% of patients, most commonly lymphopenia (in 86%), leukopenia (in 19%), esophagitis (in 10%), and esophageal fistula (in 10%). One patient died from treatment-related pneumonitis. Immune-related adverse events occurred in 69% of patients, most commonly hypothyroidism (31%), rash (29%), and hypertriglyceridemia (24%).
The investigators concluded, “Combining toripalimab with definitive chemoradiotherapy provided encouraging activity and acceptable toxicity in patients with locally advanced esophageal squamous cell carcinoma, and this regimen warrants further investigation.”
Mian Xi, MD, of the Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the National Natural Science Foundation of China and Sci-Tech Project Foundation of Guangzhou. For full disclosures of the study authors, visit thelancet.com.
