Abstract LBA25
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.
Resources from the same session
LBA26 - Neoadjuvant chemotherapy with CAPOX versus chemoradiation for locally advanced rectal cancer with uninvolved mesorectal fascia (CONVERT): Final results of a phase III trial
Presenter: Pei-Rong Ding
Session: Proffered Paper session 1 - Gastrointestinal tumours, lower digestive
Resources:
Abstract
Slides
Webcast
Invited Discussant LBA25 and LBA26
Presenter: Karin Haustermans
Session: Proffered Paper session 1 - Gastrointestinal tumours, lower digestive
Resources:
Slides
Webcast
Q&A
Presenter: All Speakers
Session: Proffered Paper session 1 - Gastrointestinal tumours, lower digestive
Resources:
Webcast
549O - Adagrasib with or without cetuximab in patients with KRASG12C-mutated colorectal cancer (CRC): Analysis of tumor biomarkers and genomic alterations
Presenter: Meredith Pelster
Session: Proffered Paper session 1 - Gastrointestinal tumours, lower digestive
Resources:
Abstract
Slides
Webcast
550O - Safety and efficacy of D-1553 in combination with cetuximab in KRAS G12C mutated colorectal cancer (CRC): A phase II study
Presenter: Rui-Hua Xu
Session: Proffered Paper session 1 - Gastrointestinal tumours, lower digestive
Resources:
Abstract
Slides
Webcast
551O - Impact of baseline molecular alterations on the efficacy of tucatinib (TUC) plus trastuzumab (Tras) for HER2+, RAS WT metastatic CRC (mCRC) in MOUNTAINEER
Presenter: John Strickler
Session: Proffered Paper session 1 - Gastrointestinal tumours, lower digestive
Resources:
Abstract
Slides
Webcast
Invited Discussant 549O, 550O and 551O
Presenter: Rodrigo Dienstmann
Session: Proffered Paper session 1 - Gastrointestinal tumours, lower digestive
Resources:
Slides
Webcast
Q&A
Presenter: All Speakers
Session: Proffered Paper session 1 - Gastrointestinal tumours, lower digestive
Resources:
Webcast