In a Chinese single-center phase II trial (SPRING-01) reported in The Lancet Oncology, Tian et al found that the addition of the PD-1 inhibitor sintilimab to chemotherapy following short-course radiotherapy as part of total neoadjuvant treatment significantly improved the pathologic complete response rate in patients with locally advanced rectal cancer.
As stated by the investigators, “Neoadjuvant short-course radiotherapy combined with chemotherapy as total neoadjuvant therapy increases the pathologic 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.”
Study Details
In the open-label trial, 98 patients with newly diagnosed disease from Shandong Provincial Hospital were randomly assigned between October 2021 and September 2023 to receive short-course radiotherapy (5 × 5 Gy over 5 days) followed by six cycles of capecitabine plus oxaliplatin (oxaliplatin at 130 mg/m² on day 1 and capecitabine at 1,000 mg/m² twice daily on days 1–14 of each 3-week cycle) with (n = 49) or without (n = 49) sintilimab at 200 mg/m² on day 1 of each 3-week cycle, starting 1 week after completion of radiotherapy. Total mesorectal excision was performed 2 to 3 weeks after completion of total neoadjuvant therapy. The primary outcome measure was pathologic complete response in the intention-to-treat population.
Key Findings
Pathologic complete response was achieved in 29 patients (59.2%, 95% confidence interval [CI] = 45.4%–72.9%) in the sintilimab group vs 16 patients (32.7%, 95% CI = 19.5%–45.8%) in the control group (P = .015).
Postoperative complications occurred in 11 (24%) of 45 patients in the sintilimab group who underwent surgery and in 5 (11%) of 44 in the control group who underwent surgery.
The most common treatment-related adverse events of any grade in the sintilimab group and the control group were thrombocytopenia (37% vs 53%), leukopenia (39% vs 53%), and anemia (55% vs 67%). Grade 3 to 4 treatment-related adverse events were observed in 33% vs 35% of patients, most commonly thrombocytopenia (12% vs 22%). Immune-related adverse events occurred in 36% of patients in the sintilimab group, most commonly dermatitis (8%) and kidney injury (8%). No treatment-related deaths were observed.
The investigators concluded: “In patients with locally advanced rectal cancer, short-course radiotherapy combined with sintilimab and capecitabine–oxaliplatin as a total neoadjuvant treatment significantly increased the [pathologic complete response] rate while maintaining a manageable safety profile. These findings suggest that this regimen might be a promising neoadjuvant treatment approach for locally advanced rectal cancer.”
Changqing Jing, MD, of the Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by The National Natural Science Foundation of China, Natural Science Foundation of Shandong Province, Innovent Biologics, and others. For full disclosures of all study authors, visit thelancet.com.
