LBA25 - Neoadjuvant short-course radiotherapy followed by camrelizumab plus chemotherapy versus long-course chemoradiotherapy followed by chemotherapy in locally advanced rectal cancer: A randomized phase III trial (UNION)

Background

Based on the results of pre-clinical research and our phase II study, we conducted a randomized, multicenter, open-label phase III study to compare the efficacy and safety of short-course radiotherapy (SCRT) followed by immunochemotherapy versus long-course chemoradiotherapy (LCRT) followed by chemotherapy for perioperative treatment of locally advanced rectal cancer (LARC).

Methods

Patients (pts) with T3-4 or N⁺ rectal adenocarcinoma, where the lower edge of the tumor was ≤ 10 cm from the anal verge, were randomly assigned to either Arm A or B in a 1:1 ratio. Stratification was based on clinical T stage (≤ T3 vs. T4) and N stage (N0 vs. N⁺), and pts received SCRT or LCRT, followed by 2 cycles of camrelizumab (CAM) + CAPOX or CAPOX, respectively. Total mesorectal excision (TME) was performed subsequently, with an additional 6 cycles of CAM + CAPOX followed by CAM for up to 1 year in Arm A, and 6 cycles of CAPOX in Arm B. Primary endpoint was the independent review committee (IRC)-assessed pCR rate (ypT0N0). Secondary endpoints tested hierarchically were 3-year EFS rate and OS.

Results

Between July 2021 and March 2023, 231 pts were randomly assigned to Arm A (n=113) and Arm B (n=118). In Arm A, 112 pts received SCRT, 107 completed neoadjuvant therapy, and 104 underwent TME. In Arm B, 115 pts received LCRT, 109 completed neoadjuvant therapy, and 99 underwent TME. The IRC-assessed pCR rate in the ITT populations was significantly improved in Arm A (39.8% [95% CI 30.7-49.5]) versus Arm B (15.3% [95% CI 9.3-23.0]), with an odds ratio of 3.7 ([95% CI 2.0-6.9], p<0.001), meeting the primary endpoint. Subgroup analysis showed consistently positive results across all subgroups. In the surgical population, the R0 resection rate was 96.2% in Arm A and 97.0% in Arm B. Postoperative complications occurred in 38.1% of pts in Arm A versus 40.8% in Arm B. Grade ≥ 3 TRAEs were observed in 29.2% of pts in Arm A and 27.2% in Arm B throughout the treatment. Long-term survival outcomes are currently being monitored.

Conclusions

SCRT followed by CAM and chemotherapy demonstrated a superior pCR rate with acceptable tolerance compared to LCRT followed by chemotherapy for LARC.

Clinical trial identification

NCT04928807.

Editorial acknowledgement

Legal entity responsible for the study

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.

Funding

Jiangsu Hengrui Pharmaceuticals, Shanghai, China.

Disclosure

F. Zhao: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals Co., Ltd.. C. Ma: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals Co., Ltd.. F. Cheng: Financial Interests, Personal, Full or part-time Employment: Jiangsu Hengrui Pharmaceuticals Co., Ltd.. All other authors have declared no conflicts of interest.