Total neoadjuvant therapy (TNT) with modified oxaliplatin, irinotecan, leucovorin, and fluorouracil (mFOLFIRINOX) improves upon standard care in patients with locally advanced rectal cancer, according to research presented at the ASCO Annual Meeting 2023.1
Updated results from the PRODIGE 23 trial showed that neoadjuvant mFOLFIRINOX, followed by chemoradiotherapy, surgery, and adjuvant chemotherapy significantly improved survival outcomes when compared to standard chemoradiotherapy, surgery, and adjuvant chemotherapy.
TNT with mFOLFIRINOX “should be considered one of the best options of care” in patients with locally advanced rectal cancer, said study presenter Thierry Conroy, MD, of Institut de Cancérologie de Lorraine in Vandoeuvre-Lès-Nancy, France.
Dr Conroy noted that the phase 3 PRODIGE 23 trial (ClinicalTrials.gov Identifier: NCT01804790) included 461 patients with locally advanced rectal cancer. They were randomly assigned to standard care (n=230) or TNT with mFOLFIRINOX (n=231). Baseline characteristics were well balanced between the arms.
Standard care consisted of preoperative chemoradiotherapy (with capecitabine), total mesorectal excision, and adjuvant treatment with leucovorin calcium, fluorouracil, and oxaliplatin (mFOLFOX6) for 12 cycles or capecitabine for 8 cycles. Patients in the mFOLFIRINOX arm received mFOLFIRINOX for 6 cycles, the same chemoradiotherapy regimen, total mesorectal excision, and mFOLFOX6 for 6 cycles or capecitabine for 4 cycles.
Prior results from this trial showed that mFOLFIRINOX improved disease-free survival (DFS) at 3 years.2 That benefit proved durable at 7 years, Dr Conroy said.1
The 7-year DFS rate was 67.6% in the mFOLFIRINOX arm and 62.5% in the standard care arm. This translated to a 5.73-month benefit in DFS for the mFOLFIRINOX arm over 7 years (P =.048).
The 7-year metastasis-free survival rate was 73.6% in the mFOLFIRINOX arm and 65.4% in the standard care arm. This translated to a 7.1-month benefit in metastasis-free survival for the mFOLFIRINOX arm over 7 years (P =.011).
“[E]ach year, patients benefit from 1 month more without metastasis,” Dr Conroy said.
There was an improvement in overall survival (OS) with mFOLFIRINOX as well. The 7-year OS rate was 81.9% in the mFOLFIRINOX arm and 76.1% in the standard care arm. This translated into a 4.37-month OS benefit for the mFOLFIRINOX arm over 7 years (P =.033).
Dr Conroy said the safety profile of TNT with mFOLFIRINOX was unchanged from prior results, and there was no increase in local recurrences in the mFOLFIRINOX arm.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
1. Conroy T, Etienne P-L, Rio E, et al. Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiation in patients with locally advanced rectal cancer: 7-year results of PRODIGE 23 phase III trial, a UNICANCER GI trial. ASCO 2023. June 2-6, 2023. Abstract LBA3504.
2. Conroy T, Bosset JF, Etienne PL, et al. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): A multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(5):702-715. doi:10.1016/S1470-2045(21)00079-6