RESUMEN
BACKGROUND: Toripalimab is a PD-1 inhibitor that is approved for the treatment of advanced oesophageal squamous cell carcinoma, but its efficacy in locally advanced disease is unclear. We administered toripalimab with definitive chemoradiotherapy to patients with unresectable locally advanced oesophageal squamous cell carcinoma, and aimed to investigate the activity and safety of this regimen, and potential biomarkers. METHODS: EC-CRT-001 was a single-arm, phase 2 trial done at Sun Yat-sen University Cancer Center (Guangzhou, China). Patients aged 18-70 years with untreated, unresectable, stage I-IVA oesophageal squamous cell carcinoma, with an ECOG performance status of 0-2, and adequate organ and bone marrow function were eligible for inclusion. Patients received concurrent thoracic radiotherapy (50·4 Gy in 28 fractions), chemotherapy (five cycles of weekly intravenous paclitaxel [50 mg/m2] and cisplatin [25 mg/m2]), and toripalimab (240 mg intravenously every 3 weeks for up to 1 year, or until disease progression or unacceptable toxicity). The primary endpoint was the complete response rate at 3 months after radiotherapy by investigator assessment. Secondary endpoints were overall survival, progression-free survival, duration of response, quality of life (not reported here), and safety. All enrolled patients were included in the activity and safety analyses. The trial is registered with ClinicalTrials.gov, NCT04005170; enrolment is completed and follow-up is ongoing. FINDINGS: Between Nov 12, 2019, and Jan 25, 2021, 42 patients were enrolled. The median age was 56 years (IQR 53-63), 39 (93%) of 42 patients had stage III or IVA disease, and 32 (76%) patients were male and 10 (24%) were female. 40 (95%) of 42 patients completed the planned chemoradiotherapy and 26 (62%; 95% CI 46-76) of 42 had a complete response. The median duration of response was 12·1 months (95% CI 5·9-18·2). After a median follow-up of 14·9 months (IQR 11·9-18·4), 1-year overall survival was 78·4% (95% CI 66·9-92·0) and 1-year progression-free survival was 54·5% (41·3-72·0). The most common grade 3 or worse adverse event was lymphopenia (36 [86%] of 42). One (2%) patient died from treatment-related pneumonitis. INTERPRETATION: Combining toripalimab with definitive chemoradiotherapy provided encouraging activity and acceptable toxicity in patients with locally advanced oesophageal squamous cell carcinoma, and this regimen warrants further investigation. FUNDING: National Natural Science Foundation of China and Sci-Tech Project Foundation of Guangzhou. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.