Abstract 252P
Background
Neoadjuvant chemoradiotherapy combined with immunotherapy can significantly increase the pCR rate, and becomes the current research hotspot. Sufficient tumor regression may provide more opportunities for R0 resection and W&W for patients who are initially diagnosed with non-radical resection. Therefore, we designed this study to provide sufficient evidence for the efficacy and safety of neoadjuvant therapy for PD-1 in the above patients.
Methods
Patients, aged from 18 to 80, pathologically diagnosed tubular adenocarcinoma, pMMR/MSS, and “Bad” or “Ugly” (according to ESMO Rectal Cancer Guidelines, 2017) LARC below peritoneal reflux are included. Patients receive neoadjuvant chemoradiotherapy (50Gy/25f with concurrent oral capecitabine) followed by 1 to 6 cycles of consolidation therapy with CapeOX in combination with sintilimab. The main endpoints are the incidence of grade ≥3 TRAEs and the CR rate. The number of cycles of consolidation therapy ≤ 3 is defined as ‘Semi’ group, others is defined as ‘Full’ group.
Results
From 06/2021 to 11/2023, a total of 45 patients were recruited; 8 were excluded due to mismatch and 2 were lost to follow-up. As of 26/03/2024, 35 patients were available for analysis with a median follow-up of 5.37 (0.33∼28.47) months. The median age was 59 (34∼74), and 67.57% were male. The median distance of the lower edge of the tumor from the anal verge was 4.2 (0∼9) cm. The overall CR rate was 51.43%. 23 underwent surgery, the pCR rate was 26.09%, and R0 resection rate was 86.96%. 12 patients opted for W&W due to cCR, 10 ‘Full’ arm and 2 from ‘Semi’. The incidence of grade 3 TRAEs was 70.27% (26/37) with lymphopenia being the most common (22/26), and was not related to the number of cycles of treatment (‘Semi’ vs. ‘full’ group, p = 0.72). Interestingly, neoadjuvant radiotherapy was able to significantly reduce the lymphocyte count (p < 0.001) which lasts until the period of consolidation therapy. Grades 2∼3 immunotherapy-related AEs were observed in 8.11% of patients. No grades 4–5 TRAEs were observed.
Conclusions
Our therapeutic strategy is shows good tumor regression activity and tolerable. The ‘full’ group was more advantageous in shrinkage of primary tumor but did not increase the rate of serious adverse events.
Clinical trial identification
NCT04906044.
Legal entity responsible for the study
The authors.
Funding
This trial was supported by the National Natural Science Foundation of China under Grant number 82272738.
Disclosure
All authors have declared no conflicts of interest.