The Lancet. Oncology
Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy versus standard of care for locally advanced rectal cancer (UNION): a prespecified interim analysis of a multicentre, open-label, randomised, phase 3 trial
By Tao K, Lin Z, Zhang P and 22 others.
Abstract
Background
To our knowledge, UNION is the first phase 3 trial to assess a neoadjuvant strategy incorporating radiotherapy, immunotherapy, and chemotherapy compared with standard care in patients with locally advanced rectal cancer, which reported positive results for the primary endpoint (blinded independent review committee [BIRC]-assessed pathological complete response rate; 39·8% vs 15·3%). Here, we present a prespecified interim analysis of event-free survival.
Methods
This open-label, randomised, phase 3 trial was conducted at nine hospitals in China. Eligible patients were aged 18-75 years with untreated cT3-4 or N+ rectal adenocarcinoma (≤10 cm distance from the anal verge) and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1; stratified by clinical T stage and N stage), using permuted blocks, to receive neoadjuvant short-course radiotherapy (25 Gy in five fractions) followed by two cycles of intravenous camrelizumab (200 mg on day 1) plus CAPOX (oral capecitabine 1000 mg/m2 twice daily on days 1-14 and intravenous oxaliplatin 130 mg/m2 on day 1; experimental group) or long-course chemoradiotherapy (50·4 Gy in 28 fractions with concurrent oral capecitabine 825 mg/m2 twice daily) followed by two cycles of CAPOX (standard-of-care group). After surgery, both groups received six cycles of adjuvant CAPOX, and the experimental group additionally received adjuvant camrelizumab for up to 15 cycles. The primary endpoint was BIRC-assessed pathological complete response rate in the intention-to-treat population, which has been previously reported. Here, we performed a prespecified interim analysis of investigator-assessed event-free survival (one of the key secondary endpoints, defined as time from randomisation to radiographic progression precluding surgery, local recurrence or distant metastasis, or death) in the intention-to-treat population (all randomly assigned patients) with a boundary of a two-sided p values less than 0·0102. Safety was evaluated in all patients who received at least one dose of the study treatment according to the assigned regimen. The study was registered with ClinicalTrials.gov, NCT04928807, and is active, but no longer recruiting.