What are the results of the PRODIGE 23 (Programme de Recherche sur le Diagnostic et la Guérison de l'Endométriose 23) trial?

From the Guidelines

The PRODIGE 23 trial demonstrated that total neoadjuvant therapy (TNT) is superior to standard chemoradiotherapy for locally advanced rectal cancer, with improved pathologic complete response (pCR) and overall survival (OS) rates. The trial showed that giving induction oxaliplatin, irinotecan, leucovorin, and fluorouracil (FOLFIRINOX), followed by chemoradiotherapy, improved outcomes compared to standard neoadjuvant chemoradiotherapy 1.

Key Findings

• The PRODIGE 23 trial used a preoperative treatment consisting of induction FOLFIRINOX, followed by chemoradiotherapy 1.
• A meta-analysis of four phase III RCTs, including PRODIGE 23, found that TNT significantly improved pCR and OS rates, but not disease-free survival (DFS) rates, compared to standard neoadjuvant chemoradiotherapy 1.
• The trial results suggest that TNT may be a beneficial approach for patients with locally advanced rectal cancer, particularly those with high-risk features.

Treatment Approach

• The TNT approach used in the PRODIGE 23 trial consisted of induction FOLFIRINOX, followed by chemoradiotherapy, and then surgery 1.
• This approach allows for earlier delivery of systemic therapy to address potential micrometastatic disease and may increase the likelihood of tumor downstaging before surgery.

Toxicity and Quality of Life

• The trial found that grade 3 to 4 treatment-related adverse events (AEs) were significantly higher in the TNT group, although the heterogeneity in this analysis was high 1.
• However, the rate of acute toxicity was higher in the CRT group versus TNT in the POLISH II study, which may be explained by the shorter duration of neoadjuvant chemotherapy delivered in the TNT arm 1.

From the Research

Results of the PRODIGE 23 Trial

• The PRODIGE 23 trial compared neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy to standard-of-care preoperative chemoradiotherapy in patients with locally advanced rectal cancer 2.
• The trial found that neoadjuvant chemotherapy with FOLFIRINOX improved disease-free survival rates at 3 years, with a rate of 76% compared to 69% in the standard-of-care group 2.
• The most common grade 3-4 adverse events during neoadjuvant chemotherapy were neutropenia and diarrhea, while during chemoradiotherapy, the most common grade 3-4 adverse event was lymphopenia 2.
• A subsequent analysis of the trial found that neoadjuvant chemotherapy with FOLFIRINOX improved health-related quality of life outcomes, including reduced tumor symptoms and improved emotional functioning 3.
• Long-term results of the trial showed that total neoadjuvant therapy with mFOLFIRINOX improved overall survival, disease-free survival, and metastasis-free survival compared to standard-of-care preoperative chemoradiotherapy 4.

Key Findings

• Neoadjuvant chemotherapy with FOLFIRINOX improved disease-free survival rates at 3 years 2.
• Neoadjuvant chemotherapy with FOLFIRINOX improved health-related quality of life outcomes, including reduced tumor symptoms and improved emotional functioning 3.
• Total neoadjuvant therapy with mFOLFIRINOX improved overall survival, disease-free survival, and metastasis-free survival compared to standard-of-care preoperative chemoradiotherapy 4.
• The safety profile of neoadjuvant chemotherapy with FOLFIRINOX was manageable, with common adverse events including neutropenia, diarrhea, and lymphopenia 2, 4.

Comparison to Other Studies

• The results of the PRODIGE 23 trial are consistent with other studies that have shown improved outcomes with total neoadjuvant therapy in locally advanced rectal cancer 5.
• The trial's findings support the use of neoadjuvant chemotherapy with FOLFIRINOX as a treatment option for patients with locally advanced rectal cancer 2, 4.