Short-course radiotherapy then camrelizumab and CAPOX improved event-free survival in rectal cancer

Design

Phase 3, randomised, open-label; prespecified interim analysis

Population

231 patients with locally advanced rectal cancer, 9 centres in China

Primary outcome

3-year event-free survival (key secondary endpoint)

Effect

91.3% vs 77.4%; HR 0.33 (0.15–0.71)

UNION, an open-label phase 3 trial at nine Chinese hospitals, randomised 231 patients aged 18–75 with untreated cT3–4 or node-positive rectal adenocarcinoma within 10 cm of the anal verge. The experimental arm received short-course radiotherapy (25 Gy in five fractions), then two cycles of the PD-1 inhibitor camrelizumab with CAPOX. The control arm received long-course chemoradiotherapy with capecitabine, then two cycles of CAPOX. Both had surgery and adjuvant CAPOX; the experimental arm also received adjuvant camrelizumab. The trial had already reported higher pathological complete response (39.8% vs 15.3%).

This prespecified interim analysis, published in The Lancet Oncology on 25 October, reports event-free survival after a median of about three years: 91.3% against 77.4% (HR 0.33, 95% CI 0.15–0.71). Severe haematological toxicity was similar or lower in the experimental arm; serious treatment-related events were 19% against 13%. One treatment-related death occurred, from chemotherapy-related sepsis.

The important caveat is the comparator. Long-course chemoradiotherapy with only two cycles of consolidation is no longer the most intensive standard; total neoadjuvant therapy regimens deliver more chemotherapy before surgery. The trial was open label, investigator-assessed for this endpoint, almost entirely Han Chinese, and included patients regardless of mismatch repair status. Camrelizumab is not widely available outside China.

• Check mismatch repair status in every rectal cancer before planning neoadjuvant treatment.
• Short-course radiotherapy followed by systemic therapy is an established framework; adding immunotherapy to it remains investigational for proficient MMR tumours.
• Interpret UNION against total neoadjuvant therapy, which was not the comparator.
• Event-free survival is a secondary endpoint at interim analysis; overall survival data are awaited.

Why it matters

It suggests immunotherapy may improve outcomes in rectal cancer beyond the mismatch-repair-deficient minority.

Don't overread it

The control arm was not modern total neoadjuvant therapy, and this is an interim secondary endpoint in an open-label trial.

The statistics, in plain English

A hazard ratio of 0.33 means about a two-thirds lower rate of recurrence, progression or death over follow-up. With 231 patients and few events, the interval is wide (0.15–0.71), so the true effect could be much smaller.

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