LBA21 Neoadjuvant mFOLFIRINOX and preoperative chemoradiation (CRT) versus preoperative CRT in patients with T3-4 rectal cancer: Surgical and quality of life results of PRODIGE 23 phase III trial

PRODIGE 23, a phase III clinical trial, investigated the role of neoadjuvant mFOLFIRINOX before preoperative chemoradiation (CRT), with TME-surgery and adjuvant chemotherapy (CT) in resectable T3-4 rectal cancer. Eligible pts had cT3-T4 M0 rectal cancers, <76 years, and WHO PS ≤1. Primary endpoint was 3-yr DFS. Secondary endpoints were ypT0N0 rate, OS, metastasis-free survival (MFS) and QoL assessed with EORTC QLQ-C30 and QLQ-CR29. 460 pts were needed to observe 136 events to increase 3-year DFS from 75% to 85% (HR=0.56). Arm A pts received preop CRT (50 Gy, 2 Gy/fr + capecitabine), surgery, then adjuvant CT for 6 mos. Arm B pts received 6 cycles of mFOLFIRINOX, followed by the same preop CRT, surgery and 3 mos of adjuvant CT. Adjuvant CT consisted of mFOLFOX6 or capecitabine. (ITT) From 2012 to 2017, 230/231 pts were randomly assigned in Arm A/B. Median follow-up was 46.5 mos and 136 DFS events occurred. Main results are reported in the table below. Time to QoL deterioration ≥ 10 points was significantly longer in Arm A for chemotherapy symptoms (hair loss, fatigue, nausea/vomiting, appetite loss, diarrhea, dry mouth, taste) and worry about weight, and was significantly longer in Arm B for functional outcomes as dysuria (HR 0.61, p<0.01), buttock pain (HR 0.7, p=0.01), fecal incontinence (HR 0.73, p=0.05), sore skin (HR 0.67, p<0.01), bowel embarrassment (HR 0.73, p=0.05) and impotence in men (HR 0.64, p<0.01).Table:Control arm, %Experimental arm, %HR and p values3yr DFS68.575.70.69 (0.49-0.097), P=0.0343 yr MFS71.778.80.64 (0.44-0.93), P<0.02Primary tumor resection rate93.592.2NsType of resection - Low anterior or intersphincteric - Abdominoperineal85.1 1485.9 14.1NsTME, complete mesorectum94.996.3NsPostoperative mortality2.80P=0.03Overall morbidity31.229.3NsMedian hospital stay, days1211NsMedian n0 of postop RBCs00NsypT0N012.127.8P<0.001R0/ R1-R294.4/5.695.3/4.7Ns Open table in a new tab Neoadjuvant mFOLFIRINOX plus CRT is safe, preserves the quality of resection and significantly increased ypCR rate, DFS, and MFS. Patients treated with neoadjuvant chemotherapy had more symptoms during chemotherapy, but benefits from longer time to QoL deterioration for rectal functional outcomes.