In a Chinese phase II trial (TORCH) reported in the Journal of Clinical Oncology, Xia et al found that integration of the PD-1 inhibitor toripalimab into total neoadjuvant therapy was associated with good outcomes in patients with mismatch repair–proficient or microsatellite-stable (pMMR/MSS) locally advanced rectal cancer.
Study Details
In the multicenter trial, 121 evaluable patients were randomly assigned between May 2021 and September 2022 to receive either:
- Short-course radiotherapy (25 Gy in 5 fractions) followed by six 21-day cycles of consolidation immunochemotherapy with toripalimab at 240 mg on day 1, oxaliplatin at 130 mg/m2 on day 1, and capecitabine at 1,000 mg/m2 twice daily on days 1 to 14 (group A, n = 62)
- Two cycles of induction immunochemotherapy followed by short-course radiotherapy and four cycles of immunochemotherapy (group B, n = 59).
Patients underwent total mesorectal excision or “watch-and-wait” based on tumor response. The primary endpoint of the trial was complete response, including pathologic complete response after surgery and clinical complete response in cases of watch-and-wait. Strategies were deemed successful if a threshold complete response rate of 40% were reached, compared with historical data indicating a rate of 25% after conventional total neoadjuvant treatment.
Key Findings
Median follow-up was 19 months. Complete response was observed in 56.5% of patients in group A (P < .001 vs threshold) and in 54.2% of patients in group B (P < .001 vs threshold).
Among 35 patients with a complete response in group A, 20 had a pathologic complete response and 15 who underwent watch-wand-wait had a continuous clinical complete response. Among 32 patients with a complete response in group B, 17 had a pathologic complete response and 15 who underwent watch-and-wait had a continuous clinical complete response.
Grade 3 or 4 adverse events occurred in 45.2% of patients in group A and 42.4% of group B, most commonly thrombocytopenia (24.2% vs 33.9%) and neutropenia (11.3% vs 5.1%).
The investigators concluded, “The immunotherapy-based total neoadjuvant therapy regimens remarkably improved complete response rates in pMMR/MSS locally advanced rectal cancer compared with [the] historical benchmark with acceptable toxicity. Upfront [short-course radiotherapy] followed by immunochemotherapy was selected for future definitive study.”
Zhen Zhang, MD, PhD, of the Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Natural Science Foundation of China. For full disclosures of the study authors, visit ascopubs.org.
