Upfront modified FOLFOXIRI plus panitumumab improves OS in RAS/BRAF wild-type mCRC

ASCO 2025

Published: 2 Jun 2025

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Dr Veronica Conca - University of Pisa, Pisa, Italy

Dr Veronica Conca talks to ecancer at ASCO 2025 about data she presented from the phase III TRIPLETE study.

This evaluated whether intensifying first-line chemotherapy with modified FOLFOXIRI plus panitumumab (Pan) improved outcomes over standard FOLFOX/Pan in patients with unresectable RAS and BRAF wild-type metastatic colorectal cancer (mCRC).

Although the intensified regimen did not enhance response rate or progression-free survival (PFS) and was associated with greater gastrointestinal toxicity, overall survival (OS) was significantly longer in the FOLFOXIRI/Pan group, with a median OS of 41.1 months compared to 33.3 months in the FOLFOX/Pan group (HR: 0.79; p = 0.049).

These findings suggest that despite similar initial treatment activity, the intensified regimen provides a meaningful survival benefit, likely driven by improved post-progression outcomes.

The TRIPLETE study, a pahse 2 study, intensified treatment in RAS and BRAF wildtype metastatic colorectal cancer. We know that doublet chemotherapy, FOLFOX or FOLFIRI, in combination with an anti-EGFR agent is the standard treatment for patients with these characteristics but FOLFOXIRI in RAS or BRAF-mutated colorectal cancer is a standard option in combination with bevacizumab. So we tried to intensify the treatment also in patients with RAS and BRAF wildtype metastatic colorectal cancer.

What was the methodology and what were the findings?

The study’s primary endpoint was objective response rate. So the study is powered on overall response rate. But in this final analysis we presented the overall survival data that was positive data.

What are the clinical implications of these findings?

The study unfortunately was a negative study because the primary endpoint was objective response rate. But overall survival data, that was very good because the difference between FOLFOXIRI plus panitumumab as compared to FOLFOX panitumumab in median value was 7.8 months of benefit from the triplet.

Maybe this should reopen the possibility to do triplet plus panitumumab in patients with RAS and BRAF wildtype metastatic colorectal cancer, especially if we make altogether the data from other trials that study and combine triplet plus anti-EGFR that are still ongoing that are still immature in terms of overall survival data.