AT A GLANCE

A new study published in the Lancet Oncology reports that adding sintilimab to capecitabine–oxaliplatin following radiotherapy improves the pathological complete response rate in patients with locally advanced rectal cancer, albeit with more postoperative complications.¹

“Neoadjuvant short-course radiotherapy combined with chemotherapy as total neoadjuvant therapy increases the pathological complete response rate for patients with locally advanced rectal cancer. The potential synergistic effects of combining radiotherapy and immunotherapy might benefit patients with locally advanced rectal cancer,” explain study authors Tian et al. “We aimed to compare the efficacy and safety of short-course radiotherapy followed by capecitabine–oxaliplatin chemotherapy with or without immunotherapy as total neoadjuvant therapy in patients with locally advanced rectal cancer.”

Eligible patients were randomly assigned (1:1) to receive either sintilimab plus capecitabine–oxaliplatin or capecitabine–oxaliplatin alone for the treatment of locally advanced rectal adenocarcinoma. All patients received short-course radiotherapy (5 × 5 Gy over 5 days), followed by six cycles of intravenous capecitabine–oxaliplatin chemotherapy (intravenous oxaliplatin 130 mg/m² over 2 h on day 1, then oral capecitabine 1000 mg/m² twice daily on Days 1–14 of each 3-week cycle) with or without intravenous sintilimab (200 mg/m² on day 1 of each 3-week cycle), starting 1 week after the completion of radiotherapy. Total mesorectal excision surgery was performed 2–3 weeks after the completion of total neoadjuvant therapy. The primary endpoint of interest was the pathological complete response rate in the intention-to-treat population.

According to the authors, a total of 98 eligible patients were randomly assigned to the sintilimab plus capecitabine–oxaliplatin group (n = 49) or the capecitabine–oxaliplatin group (n = 49). Notably, the pathological complete response rate was significantly higher in the sintilimab plus capecitabine–oxaliplatin group than in the capecitabine–oxaliplatin group (59·2%, vs. 32·7%), but postoperative complications occurred in 11 (24%) of 45 patients in the sintilimab plus capecitabine–oxaliplatin group compared to five (11%) of 44 in the capecitabine–oxaliplatin group, while treatment-related adverse events during neoadjuvant therapy occurred in 45 (92%) of 49 patients in the sintilimab plus capecitabine–oxaliplatin group and in 44 (90%) of 49 patients in the capecitabine–oxaliplatin group.

“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. These findings suggest that this regimen might be a promising neoadjuvant treatment approach for locally advanced rectal cancer,” conclude the authors.

Reference

1.     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 (July 8, 2025). Lancet Oncol.