Efficacy, Safety of Various Total Neoadjuvant Therapy Approaches Among Patients With Locally Advanced Rectal Cancer
According to results from a case series study, various total neoadjuvant therapy approaches demonstrated similar efficacy and safety outcomes among patients with locally advanced rectal cancer.
In this multicenter study, researchers collected data from 1585 patients with stage 2/3 rectal adenocarcinoma who underwent total neoadjuvant therapy with either FOLFIRINOX and FOLFOXIRI followed by long-course chemoradiotherapy (PRODIGE 23-like; n = 271), short-course radiotherapy followed by consolidation FOLFOX and CAPOX (RAPIDO-like; n = 529), induction FOLFOX and CAPOX followed by long-course chemoradiotherapy (OPRA induction-like; n = 190), or long-course chemoradiotherapy followed by consolidation FOLFOX and CAPOX (OPRA consolidation-like; n = 257).
Following total neoadjuvant therapy, 222 patients were assigned to either watch and wait (n = 192) or undergo local excision (n = 30). The primary end point was response. Key secondary end points included event-free survival (EFS), overall survival (OS), and safety.
At analysis, the pathological or clinical complete response rate was 23.2%. Local treatment failure occurred in 8.5% of patients and distant progression occurred in 16.4% of patients. The 3-year EFS rate was 68% and the 5-year OS rate was 79%. Patients treated with the PRODIGE 23-like regimen underwent more serious adverse events (23.5%) in comparison to patients treated with the RAPIDO-like regimen however, patients had better local control and survival outcomes.
For patients treated with the RAPIDO-like regimen, the hazard ratio (HR) for EFS was 0.68 (95% confidence interval [CI], 0.49 to 0.95; P = .03) and the HR for OS was 0.51 (95% CI, 0.27 to 0.97; P = .04). For patients treated with the OPRA induction-like regimen, the HR for EFS was 0.66 (95% CI, 0.44 to 0.98; P = .04). The HR for OS was 0.35 (95% CI, 0.18 to 0.70; P = .003). For patients treated with the OPRA consolidation-like regimen, the HR for EFS was 0.64 (95% CI, 0.44 TO 0.93; P = .02) and the HR for OS was 0.50 (95% CI, 0.25 to 1.00; P = .05).
“The findings of this case series study show substantial variation in the choice of the [total neoadjuvant therapy] regimen and were overall aligned with those reported in clinical trials, suggesting the efficacy of [total neoadjuvant therapy] in a clinical setting regardless of the specific regimen,” concluded Alessandro Audisio, MD, University of Turin, Turin, Italy, et al.
Source:
Audisio A, Gallio C, Velenik V, et al. Total neoadjuvant therapy for locally advanced rectal cancer. JAMA Oncol. Published online: July 10, 2025. doi: 10.1001/jamaoncol.2025.2026
