Short-course radiotherapy followed by the anti-PD-1 antibody camrelizumab and chemotherapy significantly improved event-free survival compared to a conventional regimen in patients with locally advanced rectal cancer, according to an interim analysis of the phase 3 UNION trial.

At 3 years, event-free survival was 91.3% with the experimental regimen vs 77.4% with long-course chemoradiotherapy plus chemotherapy — representing a 67% reduction in the risk for radiographic progression precluding surgery, local recurrence, distant metastasis, or death. The safety profiles were generally similar.

“This novel strategy may represent a new neoadjuvant treatment option,” researcher Zhenyu Lin, MD, of Huazhong University of Science and Technology in Wuhan, China, said during a presentation at the European Society for Medical Oncology (ESMO) Annual Meeting 2026 in Madrid, Spain.

However, the findings, which were simultaneously published in The Lancet Oncology, leave open questions about the role for immunotherapy in this setting.

Trial discussant David Tougeron, MD, PhD, of Poitiers University Hospital in Poitiers, France, cautioned that this experimental regimen was not compared with contemporary total neoadjuvant therapy (TNT) and that differences between the treatment groups made it difficult to determine the specific contribution of immunotherapy to patients’ improved outcomes.

In particular, the UNION’s control arm included only two cycles of preoperative capecitabine and oxaliplatin (CAPOX), whereas contemporary TNT regimens typically deliver more intensive chemotherapy before surgery. In the UNION trial, six additional cycles were planned after surgery, making the control regimen more consistent with a conventional perioperative approach than with contemporary TNT.

A Broader Role for Immunotherapy?

TNT based on long-course chemoradiotherapy or short-course radiotherapy combined with chemotherapy is now a standard of care for patients with locally advanced rectal cancer, particularly those with high-risk disease. Yet roughly 30% of patients experience recurrence or distant metastasis within 3 years.

Immunotherapy in rectal cancer has largely been confined to patients with deficient mismatch repair or microsatellite instability-high disease. However, more than 90% of colorectal cancers have proficient mismatch repair (pMMR) or are microsatellite-stable (MSS) and respond poorly to immune checkpoint inhibitor monotherapy.

Some evidence suggests that radiotherapy may enhance the antitumor immune response, potentially improving the effectiveness of immunotherapy in these patients.

The UNION was an open-label trial involving 231 patients with previously untreated, locally advanced rectal adenocarcinoma, defined as clinical T3-T4 or node-positive disease. Most patients (median age, 58 years) had pMMR tumors (93%) and high-risk disease (82%). They were randomly assigned 1:1 to one of two treatment strategies.

The experimental group received short-course radiotherapy (25 Gy in five fractions), followed by two cycles of camrelizumab plus CAPOX. Patients then underwent total mesorectal excision, followed by six planned cycles of adjuvant CAPOX plus camrelizumab, then camrelizumab maintenance.

The standard care group received conventional long-course chemoradiotherapy (50.4 Gy in 28 fractions with concurrent capecitabine), followed by two cycles of CAPOX, surgery, and six planned cycles of adjuvant CAPOX.

The UNION investigators previously reported that the experimental strategy significantly improved the pathologic complete response rate, the trial’s primary endpoint, compared with standard treatment (39.8% vs 15.3%; P < .001).

Fewer Recurrences, Similar Safety

At data cutoff for the current analysis, the median follow-up was 36.7 months in the experimental group and 34.7 months in the comparison group.

The 3-year investigator-assessed event-free survival rate was 91.3% with the experimental regimen vs 77.4% with the standard treatment (hazard ratio [HR], 0.33; P = .0029), crossing the prespecified statistical significance threshold of P < .0102, Lin reported.

The difference was largely driven by fewer recurrences and distant metastases among patients receiving the immunotherapy regimen: none had isolated local recurrences compared to four in the control group, whereas distant metastasis alone occurred in 6 vs 17 patients.

A blinded, independent review committee confirmed the event-free survival benefit, with 3-year rates of 87.2% and 73.7%, respectively (HR, 0.41). And subgroup analyses generally favored the experimental regimen, including among patients with pMMR tumors.

At 3 years, the overall survival rate was numerically higher with the experimental regimen (96.3% vs 89.8%; HR, 0.35). However, only 15 deaths had occurred, and the overall survival data remain immature. No formal statistical testing of overall survival was performed.

Among patients who underwent complete surgical resection, 3-year disease-free survival was also higher in the experimental group (92.6% vs 81.4%; HR, 0.33).

The overall safety profile was similar between groups. Grade 3 or higher treatment-related adverse events occurred in 51% of patients receiving the immunotherapy regimen and 48% of those in the control group. The most common grade 3 or higher events were largely reversible hematologic toxicities.

Just less than 10% of patients on the experimental combination developed serious immune-related adverse events, and one patient died of septic shock — which the investigators attributed to chemotherapy, not camrelizumab. There were no treatment-related deaths in the control group.

Promising but Not Practice-Changing

Camrelizumab is approved for several cancers in China but is not yet approved in the US or EU. Whether it, or other immunotherapies, deserve a broader role in rectal cancer treatment remains to be seen.

Tougeron characterized the UNION as a strong, positive trial. But he emphasized the fact that the control arm did not reflect current TNT regimens — nor did the trial incorporate contemporary organ-preservation strategies for patients who achieve a complete clinical response to neoadjuvant treatment and might be able to avoid surgery.

Tougeron also pointed out that other studies evaluating immunotherapy in patients with pMMR/MSS rectal cancer have had mixed results, further complicating the picture. For now, he said, immunotherapy cannot be considered the standard of care for these patients.

Going forward, Tougeron said that longer follow-up is essential to establish whether the event-free survival benefit in UNION translates into improved overall survival. Data on patients’ quality of life are another important piece.

The UNION investigators agreed, calling for comparisons with contemporary TNT regimens, particularly those incorporating organ preservation, and validation in other populations using globally available checkpoint inhibitors.

The study was funded by the Key Clinical Research Initiative Program of Union Hospital, the National Key Technology Research and Development Programme of Hubei Province, and Jiangsu Hengrui Pharmaceuticals, which manufactures camrelizumab. Several study authors were employees of Jiangsu Hengrui Pharmaceuticals. Tougeron disclosed having consulting, advisory, or honoraria relationships with multiple pharmaceutical companies.