Results from the phase UNION Phase III trial, presented by Zhen Yu Lin at ESMO 2026, demonstrated that short-course radiotherapy followed by camrelizumab and chemotherapy significantly improved event-free survival (EFS) compared with standard long-course chemoradiotherapy and chemotherapy in patients with locally advanced rectal cancer (LARC).
At three years, event-free survival reached 91.3% with the camrelizumab-based regimen compared with 77.4% in the standard treatment group, representing a 67% relative reduction in the hazard of an event.
The findings are particularly important given the limited effectiveness of immunotherapy-based strategies in the predominantly mismatch repair-proficient (pMMR), microsatellite-stable (MSS) rectal cancer population.
Background
Despite improvements in neoadjuvant chemoradiotherapy and systemic treatment, patients with locally advanced rectal cancer remain at risk of disease recurrence and distant metastases.
Immune checkpoint inhibitors have demonstrated remarkable activity in mismatch repair-deficient rectal cancer. However, treatment options incorporating immunotherapy remain limited for patients with pMMR/MSS tumors, which account for most cases of rectal cancer.
The UNION trial investigated whether combining short-course radiotherapy, the PD-1 inhibitor camrelizumab, and chemotherapy could improve outcomes compared with conventional chemoradiotherapy followed by chemotherapy.
The study represents the first phase III randomized trial evaluating this immunotherapy-based multimodality strategy in locally advanced rectal cancer.
Study Design and Patient Population
UNION was a randomized phase III study involving 231 patients with locally advanced rectal adenocarcinoma, defined as cT3–4 or node-positive disease, with tumors located within 10 cm of the anal verge.
Between July 2021 and March 2023, patients were randomized 1:1 into two treatment groups.
Experimental group (113 patients)
Patients received short-course radiotherapy (SCRT) at 25 Gy in five fractions, followed by two cycles of neoadjuvant CAPOX chemotherapy and six cycles of adjuvant CAPOX.
Camrelizumab was administered at 200 mg on day 1, beginning with CAPOX treatment and continuing through the neoadjuvant and adjuvant periods for up to 17 cycles.
Standard-of-care group (118 patients)
Patients received long-course chemoradiotherapy consisting of 50.4 Gy in 28 fractions, with concurrent capecitabine at 825 mg/m² twice daily.
This was followed by two neoadjuvant and six adjuvant cycles of CAPOX chemotherapy, without camrelizumab. The primary endpoint was pathological complete response (pCR), assessed by a blinded independent review committee.
Key secondary endpoints included investigator-assessed event-free survival and overall survival, with prespecified statistical testing. The latest analysis focused on the prespecified event-free survival endpoint.
Three-Year Event-Free Survival Results
At the October 1, 2025, data cutoff, median follow-up was 36.8 months in the experimental group and 35.6 months in the standard treatment group.
The experimental regimen significantly improved three-year event-free survival:
SCRT plus camrelizumab and CAPOX: 91.3% (95% CI, 83.9–95.4).
Standard chemoradiotherapy plus CAPOX: 77.4% (95% CI, 67.9–84.4).
The hazard ratio was 0.33 (95% CI, 0.15–0.71; P=0.0029), indicating a 67% relative reduction in the hazard of an event with the experimental treatment strategy.
The absolute difference in three-year EFS was 13.9 percentage points.
Event-free survival assessed by the blinded independent review committee also consistently favored the experimental treatment group. These findings provide strong evidence that the investigated multimodality strategy can improve disease-related outcomes in patients with locally advanced rectal cancer.
Safety and Treatment-Related Toxicity
Despite the addition of immunotherapy, rates of severe treatment-related adverse events were comparable between the two groups.
During the complete treatment period, grade 3 or higher treatment-related adverse events occurred in:
- 51.3% (59/115) of patients in the experimental group.
- 48.2% (54/112) of patients in the standard-of-care group.
The relatively similar rates suggest that the addition of camrelizumab within this treatment regimen did not result in a marked increase in the overall incidence of severe treatment-related toxicity.
However, the abstract does not provide detailed information on individual adverse events, immune-related toxicities, or treatment discontinuation.
Clinical Implications
The UNION trial represents an important development in the treatment of locally advanced rectal cancer, particularly in the context of integrating immunotherapy into neoadjuvant treatment.
The significant improvement in three-year EFS suggests that combining short-course radiotherapy with camrelizumab and CAPOX may offer a more effective approach than the evaluated conventional chemoradiotherapy regimen.
Importantly, the study investigated a treatment strategy that differed from the control group in both radiotherapy schedule and the addition of immunotherapy.
Therefore, the observed benefit cannot be attributed exclusively to camrelizumab, and the individual contributions of short-course radiotherapy and immune checkpoint inhibition cannot be separated from this comparison.
The findings are especially relevant for the pMMR/MSS population, although the supplied analysis does not report EFS separately by mismatch repair status. Further data on overall survival, pathological response, long-term toxicity, and outcomes across molecular subgroups will help define the optimal role of this treatment strategy.
Conclusion
The phase III UNION trial demonstrated a statistically significant improvement in three-year event-free survival with short-course radiotherapy followed by camrelizumab and CAPOX chemotherapy compared with long-course chemoradiotherapy and CAPOX in locally advanced rectal cancer.
Three-year EFS improved from 77.4% to 91.3% (HR 0.33; P=0.0029), without a substantial numerical increase in grade 3 or higher treatment-related adverse events.
Investigators concluded that the regimen represents a new standard-of-care option.
These findings establish an important phase III efficacy signal for immunotherapy-containing multimodality treatment in locally advanced rectal cancer, while further evaluation of long-term outcomes and patient selection remains essential.
