Neoadjuvant SCRT Combo May Prolong Survival in Advanced Rectal Cancer

At a median follow-up duration of 40.8 months, among 27 patients who received at least 1 dose of camrelizumab plus CAPOX and who underwent total mesorectal excision, the median disease-free survival (DFS) was not reached, with an estimated 3-year DFS rate of 80.2%.

Neoadjuvant short-course radiotherapy (SCRT) followed by camrelizumab (AiRuiKa) as well as oxaliplatin and capecitabine (CAPOX) benefited 3-year survival outcomes in a small cohort of patients with locally advanced rectal cancer (LARC), according to results from a phase 2 trial (NCT04231552) published in BMC Medicine.

At a median follow-up duration of 40.8 months (IQR, 40.3-44.3), among 27 patients who received at least 1 dose of camrelizumab plus CAPOX and who underwent total mesorectal excision (TME), the median disease-free survival (DFS) was not reached (NR; 95% CI, 39.7-NR), with an estimated 3-year DFS rate of 80.2% (95% CI, 58.6%-91.3%). Additionally, 2 (6.7%) of the 30 enrolled patients had died, with an immature median overall survival (OS). The estimated 3-year rate OS rate was 93.3% (95% CI, 75.9%-98.3%) among this patient group.

Furthermore, subgroup analyses showed patients who had attained a pathological complete response (pCR) experienced enhanced 3-year DFS outcomes at 100% (95% CI, 100%-100%) vs 63.5% (95% CI, 33.1%-83.0%) in those who did not (P = .018). A 3-year DFS advantage was also seen among those with postoperative pathological node-negative status at 94.4% (95% CI, 66.6%-99.2%) with pN0 vs 50% (95% CI, 15.2%-77.5%) in those with node-positive status (P = .003).

Additional 3-year DFS benefit was seen in patients with negative baseline circumferential resection margin (CRM) status at 100% (95% CI, 100%-100%) vs 69.5% (95% CI, 41.3%-86.1%) in those with CRM-positive status (P = .036). Finally, a 3-year DFS benefit was seen in patients with negative extramural venous invasion (EMVI) at 100% (95% CI, 100%-100%) vs 54.5% (95% CI, 22.9%-78.0%) in those with positive EMVI (P = .036).

“With over 3 years of follow-up, neoadjuvant SCRT followed by camrelizumab and CAPOX regimen was associated with promising survival outcomes in patients [with LARC],” Zhenyu Lin, researcher at the Institute of Radiation Oncology at the Union Hospital of Tongji Medical College in Wuhan, China, wrote in the publication with study coinvestigators. “These [data] suggested that this regimen may be a promising therapeutic option, especially with the potential to address an unmet need for patients with MSS [microsatellite-stable] tumors.”

The single-arm phase 2 trial enrolled patients aged 18 to 75 years with previously untreated LARC with an inferior margin of 10 cm or fewer from the anal verge and an ECOG performance status of 0 or 1 who received treatment at Tongji Medical Hospital. Patients received five 5-Gy doses of SCRT over 5 days. Intravenous camrelizumab at 200 mg was administered after 1 week of SCRT. A CAPOX regimen, consisting of 130 mg/m2 of intravenous oxaliplatin and 1000 mg/m2 of oral capecitabine administered twice daily for 2 weeks, was given every 3 weeks for 2 cycles.

TME was planned for 1 week after completion of neoadjuvant treatment, and adjuvant chemotherapy regimens were given at investigator’s discretion at 3 to 4 weeks after surgery.

A total of 26 patients (86.7%) had positive lymph nodes, of whom 10 (33.3%) had N2 disease. Twenty-one (70.0%) had CRM, 12 (40.0%) had EMVI, and half (50.0%) had the lower edge of the tumor fewer than 5 cm from the anal verge. A total of 28 patients (93.3%) had MSS disease, and 20 (66.7%) had a PD-L1 combined positive score of less than 1.

The primary end point of the study was the pCR rate. Secondary end points included 3-year DFS and OS, R0 resection rate, complication rate, and safety.

Of 27 patients who underwent TME, 21 (77.8%) received subsequent adjuvant CAPOX, with a median number of 4 (range, 1-6) adjuvant cycles. Two patients who received 6 cycles of adjuvant CAPOX experienced dose reductions related to weight loss and hand-foot syndrome. Additionally, 3 patients discontinued adjuvant oxaliplatin due to single instances of grade 2 thrombocytopenia, grade 2 gastrointestinal reaction, and an unknown cause. No grade 5 adverse effects or emergent toxicities were observed.

Reference

Lin Z, Zhang P, Cai M, et al. Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy for locally advanced rectal cancer: three-year survival from a phase 2 study. BMC Med. 2025;23:275. doi:10.1186/s12916-025-04087-x