7-year outcomes of PRODIGE 23 trial

Long-term outcomes of the phase 3 PRODIGE 23 trial showed that induction chemotherapy with mFOLFIRINOX before neoadjuvant chemoradiotherapy improved 7-year overall survival (OS) in patients with locally advanced rectal cancer.

Treatment of locally advanced rectal cancer with chemoradiotherapy followed by surgery and subsequent adjuvant chemotherapy controls local disease, but distant metastases remain common. Previously, both the RAPIDO (NCT01558921) and PRODIGE 23 (NCT01804790) trials reported better short-term outcomes (pCR rate of about 26%) and higher metastasis-free survival (MFS) using induction (PRODIGE 23) or consolidation (RAPIDO) chemotherapy while no significant 3-year OS improvement was observed [1–3]. Prof. Thierry Conroy (Institut de Cancérologie de Lorraine, France) presented 7-year results from PRODIGE 23 [4].

PRODIGE 23 enrolled 461 patients with locally advanced rectal cancer (cT3 or cT4, Nx, M0) who were randomised 1:1 to standard-of-care (i.e. neoadjuvant chemoradiotherapy followed by surgery and 12 cycles of adjuvant mFOLFIRINOX) or total neoadjuvant therapy (TNT; 6 cycles of neoadjuvant mFOLFIRINOX followed by neoadjuvant chemoradiotherapy, surgery, and 6 cycles of adjuvant mFOLFIRINOX). The primary endpoint was disease-free survival (DFS). Key secondary endpoints were MFS and OS. Restricted median survival time (RMST) at 7 years was chosen in the statistical analyses.

At 7 years, the cumulative incidence of local cancer recurrence was 5.3% versus 8.1% in the TNT arm versus standard-of-care arm, respectively. The cumulative incidence of metastatic disease was 20.7% versus 27.7%, respectively. The number of deaths were 18.2% versus 24.4%, respectively. The 7-year DFS rate was 67.6% versus 62.5%, resulting in an RMST of 5.73 months of DFS benefit for the TNT arm (P=0.048).

The secondary endpoint of 7-year MFS was 73.6% versus 65.4%, respectively, resulting in an RMST of 7.1 months of MFS benefit for the TNT arm (1 month of MFS benefit/year; P=0.011). The 7-year OS was 81.9% versus 76.1%, respectively, resulting in an RMST of 4.37 months benefit for the TNT arm (P=0.033; see Figure).

Figure: 7-year overall survival in the PRODIGE 23 trial [1]



CI, confidence interval; OS, overall survival; RMST, restricted median survival time; SoC, standard-of-care; TNT, total neoadjuvant therapy.

“These long-term outcomes demonstrated that induction chemotherapy with mFOLFIRINOX before neoadjuvant chemoradiotherapy improves OS of patients with locally advanced rectal cancer. Therefore, TNT with neoadjuvant mFOLFIRINOX should now be considered as one of the best options of care for these patients,” Prof. Conroy concluded.

1. Bahadoer RR, et al. Lancet Oncol. 2021;22:29–42.
2. Conroy T, et al. Lancet Oncol. 2021;22:702–715.
3. Bascoul-Molevi C, et al. Eur J Cancer. 2023;186:151–165.
4. Conroy T, 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. Abstract LBA3504, ASCO Annual Meeting 2023, 2–6 June, Chicago, USA.

 

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Posted on 2 August, 202328 March, 2024