Adding Sintilimab to Neoadjuvant Short-Course Radiotherapy Plus Chemotherapy for Newly Diagnosed Patients With Locally Advanced Rectal Cancer
According to results from the phase 2 SPRING-01 trial, the addition of sintilimab to short-course radiotherapy plus chemotherapy significantly improved pathological complete response (pCR) among newly diagnosed patients with locally advanced rectal cancer.
“Neoadjuvant short-course radiotherapy combined with chemotherapy as total neoadjuvant therapy increases the [pCR] rate for patients with locally advanced rectal cancer,” stated Feng Tian, MD, Shandong First Medical University, Jinan, Shandong, China, and coauthors. “The potential synergistic effects of combining radiotherapy and immunotherapy might benefit patients with locally advanced rectal cancer.”
In this open-label study, 98 patients were randomized on a 1-to-1 basis to receive capecitabine plus oxaliplatin either alone (n = 49) or in combination with 200 mg/m2 of sintilimab (n = 49). Patients received short-course radiotherapy (5 x 5 Gy), followed by 6 additional cycles of capecitabine plus oxaliplatin with or without sintilimab, by randomization. Surgical resection was completed within 2 to 3 weeks of neoadjuvant therapy. The primary end point was pCR rate. A key secondary end point was safety.
At a median follow-up of 25 months, the pCR rate was 29% in the sintilimab arm and 16% in the chemotherapy arm (P = .015). Postoperative complications occurred in 24% and 11% of patients, respectively. Treatment-related adverse events during neoadjuvant treatment occurred in 92% of patients in the sintilimab arm and 90% of patients in the chemotherapy arm. The most frequently observed events included thrombocytopenia, leukopenia, anemia, nausea, vomiting, and diarrhea. Grade 3/4 treatment-related thrombocytopenia occurred in 33% and 35% of patients, respectively. Serious adverse events occurred in 31% of patients in the chemotherapy plus sintilimab arm and 18% of patients in the chemotherapy arm and most frequently included thrombocytopenia. No treatment-related deaths occurred in the chemotherapy plus sintilimab arm.
“In patients with locally advanced rectal cancer, short-course radiotherapy combined with sintilimab and capecitabine–oxaliplatin as a total neoadjuvant treatment significantly increased the pathological complete response rate while maintaining manageable safety profile,” concluded Dr Tian et al. “These findings suggest that this regimen might be a promising neoadjuvant treatment approach for locally advanced rectal cancer.”
Source:
Tian F, Dai H, Sha D, et al. Total neoadjuvant treatment with short-course radiotherapy followed by sintilimab plus capecitabine–oxaliplatin versus short-course radiotherapy followed by capecitabine–oxaliplatin in patients with locally advanced rectal cancer (SPRING-01): A single-centre, open-label, phase 2, randomised controlled trial. Lancet Oncol. Published online: July 8, 2025. doi: 10.1016/S1470-2045(25)00286-4
