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

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·a clinically meaningful level vs 15·3%).

Here, we present a prespecified interim analysis of event-free survival. 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/m 2 twice daily on days 1-14 and intravenous oxaliplatin 130 mg/m 2 on day 1; experimental group) or long-course chemoradiotherapy (50·4 Gy in 28 fractions with concurrent oral capecitabine 825 mg/m 2 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. Between July 23, 2021, and March 1, 2023, 231 patients (153 [66%] males and 78 [34%] females; 227 [9a clinically meaningful level] were Han Chinese, and four [2%] were other ethnicity Chinese) were randomly assigned to the experimental group (n=113) and standard-of-care group (n=118).

As of Oct 1, 2025, the median follow-up duration was 36·7 months (IQR 32·6-39·9) in the experimental group and 34·7 months (31·1-39·1) in the standard-of-care group. The 3-year investigator-assessed event-free survival rate was 91·3% (95% CI 83·9-95·4) in the experimental group versus 77·4% (67·9-84·4) in the standard-of-care group (stratified hazard ratio 0·33 [0·15-0·71]; two-sided log-rank p=0·0029).

During the entire treatment period, the most common grade 3 or 4 treatment-related adverse events were decreased lymphocyte count (23 [20%] of 115 in the experimental group vs 31 [2a clinically meaningful level] of 112 in the standard-of-care group), decreased white blood cell count (13 [11%] vs 16 [14%]), decreased neutrophil count (13 [11%] vs 13 [12%]), and decreased platelet count (seven [6%] vs 15 [13%]). Treatment-related serious adverse events occurred in 22 (19%) versus 15 (13%) patients, with the most common being decreased platelet count (one [1%] vs six [5%]), and radiation gastroenteritis (two [2%] vs four [4%]).

Treatment-related deaths occurred in one patient in the experimental group (septic shock related to chemotherapy, but unrelated to camrelizumab) and none in the standard-of-care group.

In this interim analysis, short-course radiotherapy followed by camrelizumab and CAPOX significantly improved 3-year event-free survival in patients with locally advanced rectal cancer, with a safety profile similar to long-course chemoradiotherapy followed by CAPOX.

Comparison of this promising new treatment strategy with contemporary total neoadjuvant therapy strategies is warranted.