Three-year survival data from a phase 2 trial of neoadjuvant short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer.

e15611 Background: For locally advanced rectal cancer (LARC), short-course radiotherapy (SCRT) or long-course chemoradiotherapy combined with chemotherapy have been the established neoadjuvant treatment, but the optimal therapeutic modality is still under exploration. We previously reported the short-term results of neoadjuvant SCRT followed by chemotherapy and camrelizumab (a PD-1 inhibitor), encouragingly noting pathological complete response (pCR) in 48.1% of LARC patients (Lin Z et al. J Immunother Cancer 2021;9:e003554). Here, we report the further 3-year follow-up results. Methods: Adult patients with histologically confirmed T3-4N0M0 or T1-4N+M0 rectal adenocarcinoma were enrolled. Prior to surgery, eligible patients received 5×5 Gy SCRT, and after one week, they were treated with camrelizumab (200 mg, i.v., on day 1) plus CAPOX chemotherapy (oxaliplatin 130 mg/m 2 , i.v., on day 1 and capecitabine 1000 mg/m 2 , orally, bid, on days 1-14) in 21-day cycles for 2 cycles. Radical surgery was performed one week after the last neoadjuvant cycle. For this updated analysis, disease-free survival (DFS) and overall survival (OS) at 3 years are reported. Results: Thirty patients were enrolled and received SCRT, and all of these patients were included in this OS analysis. Among them, 27 patients received camrelizumab plus CAPOX chemotherapy, all of whom underwent surgery and were included in this DFS analysis. Of the 27 patients, 21 patients (77.8%) received at least one cycle of postoperative adjuvant chemotherapy with CAPOX regimen. With a median follow-up of 40.8 months (IQR 40.3-44.3), disease recurrence or death occurred in six (22.2%) patients. The median DFS and OS were both not reached, with the 3-year DFS and OS rates of 80.2% (95% CI 58.6-91.3) and 93.3% (95% CI 75.9-98.3), respectively. Subgroup analysis showed that patients with pCR, postoperative pathological node-negative status, PD-L1 combined positive score ≥ 1, and negative circumferential resection margin and negative extramural venous invasion by MRI at baseline had a tendency towards improved 3-year DFS and OS compared to those without these characteristics. No new or long-term safety signals were identified. Conclusions: With 3 years of extended follow-up, a favorable survival benefit was observed with neoadjuvant SCRT combined with subsequent CAPOX plus camrelizumab followed by delayed surgery in LARC patients. A randomized phase 3 trial (NCT04928807) is ongoing to confirm these results. Clinical trial information: NCT04231552 .