3576 - Clinical Benefit of Adding Irinotecan to Standard Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis

02:30pm - 03:45pm PT

Hall F

Screen: 6

POSTER

Presenter(s)

Botian Zhao, MD - The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei

B. Zhao, and F. P. Wu; The fourth hospital of hebei medical university, Shijiazhuang, Hebei, China

Purpose/Objective(s): Neoadjuvant fluorouracil-based chemoradiotherapy has been considered the standard of care for locally advanced rectal cancer. Whether addition of irinotecan will further improve clinical outcomes is still debated. The aim of this study was to evaluate the short-term efficacy, long-term survival, and safety of adding irinotecan during neoadjuvant therapy in LARC patients.

Materials/Methods: PubMed, Embase, Web of Science, Cochrane Library were searched to review prospective studies on the use of irinotecan during neoadjuvant therapy for LARC published from January 2000 to October 2024. Literatures were screened according to the inclusion and exclusion criteria, quality assessment was performed on those that met the criteria, and meta-analysis and sensitivity analysis were performed using Stata 15.0 after extracting relevant data.

Results: In the study of irinotecan's participation in neoadjuvant chemoradiotherapy, we included 25 studies with a total of 1357 LARC patients. The meta-analysis showed that the R0 resection rate was 96% (95% CI 95%-98%), the pathological complete response (pCR) rate was 21% (95% CI 17%-24%), the overall organ preservation rate was 73% (95% CI 66%-80%), and the incidence of grade =3 diarrhea and leukopenia was 12% (95% CI 9%-16%) and 8% (95% CI 7%-10%), respectively. In the study of neoadjuvant chemoradiotherapy, there were 5 randomized controlled trials. The meta-analysis showed that the addition of irinotecan improved the pCR rate, but the difference was not statistically significant (RR: 1.28, 95% CI 0.9-1.82). The addition of irinotecan did not significantly improve the short-term efficacy of neoadjuvant therapy in terms of R0 resection (RR: 0.99, 95% CI 0.88-1.13) and organ preservation (RR: 1.03, 95% CI 0.90-1.18). Regarding long-term survival, the participation of irinotecan did not provide overall survival benefits to LARC patients (HR with 5-year OS: 0.96, 95% CI 0.82-1.10, p=0.577). However, compared to using fluorouracil alone, the addition of irinotecan increased the incidence of grade =3 diarrhea (RR: 2.16, 95% CI 0.79-5.90) and leukopenia (RR: 3.61, 95% CI 1.22-10.73). Seven studies investigated the use of irinotecan during neoadjuvant sequential/induction chemotherapy. The meta-analysis showed a pCR rate of 27% (95% CI: 23%-32%), but due to the increase in irinotecan dosage and chemotherapy cycles, the incidence of grade =3 leukopenia also increased (15%, 95% CI 7%-26%).

Conclusion: This meta-analysis indicates that the addition of irinotecan in neoadjuvant chemoradiotherapy for LARC increases the pCR rate, but also leads to a higher incidence of grade =3 adverse reactions without providing significant long-term survival benefits. Compared to concurrent chemoradiotherapy combined with irinotecan, the participation of irinotecan in neoadjuvant induction/sequential chemotherapy can result in higher pCR rates; however, it also increases the incidence of grade =3 adverse reactions, such as hematological toxicity.