596P - Comparison of neoadjuvant chemoradiotherapy with CAPEOX versus single-agent capecitabine in high-risk locally advanced rectal cancer: Long-term results from a multicenter randomized controlled trial (MONT-R)

Background

The benefit of adding oxaliplatin to neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC) remains controversial. We conducted a multicenter randomized trial aimed at evaluating the value of adding oxaliplatin to nCRT in high-risk LARC patients.

Methods

LARC patients with high-risk factors (cT4 or cN2, high pathological grade, neurovascular invasion, or anal sphincter involvement) were randomized in a 1:1 ratio to receive long-course radiotherapy plus three cycles of concurrent CAPEOX or single-agent capecitabine. The primary endpoint was 3-year disease-free survival (3y-DFS). Secondary endpoints included pathological complete response (pCR) rate, CAP tumor regression grade, and treatment-related adverse reactions.

Results

From August 2017 to April 2022, 505 patients were randomized to the CAPEOX group (n=248) or the Capecitabine group (n=257). 91.5% of the CAPEOX group and 92.2% of the Capecitabine group underwent radical surgery after nCRT. Pathological examination showed no significant difference in pCR rate between the two groups (25.6% for the CAPEOX and 25.3% for the Capecitabine group, P＞0.05). However, compared with the single-agent group, a higher proportion of patients in the CAPEOX group achieved significant tumor regression (CAP 0-1) (59.0% vs. 46.8%, P=0.009). There was no significant difference in the incidence of grade 3-4 treatment-related toxicity between the CAPEOX and the Capecitabine group (46.5% vs. 39.9%, P＞0.05). After a median follow-up of 37 months, there was no significant difference in 3y-DFS between the two groups (81.7% in the CAPEOX vs. 83.5% in the Capecitabine group, P＞0.05). In the overall analysis, patients achieving CAP 0-1 had significantly better 3y-DFS than those achieving CAP 2-3 (89.0% vs. 80.9%, P=0.018).

Conclusions

We showed that adding oxaliplatin to nCRT in high-risk LARC patients may improve tumor regression with acceptable toxicities, although this may not translate into long-term oncological benefits.

Clinical trial identification

NCT 03042000.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

The work was supported by the Major Grants Program of Beijing Science and Technology Commission (No. D171100002617003) and National High Level Hospital Clinical Research Funding (No. 2022-PUMCH-C-005).

Disclosure

All authors have declared no conflicts of interest.