AT A GLANCE

A new study published in the European Journal of Cancer concludes that maintaining an adequate relative dose intensity (RDI) during first-line therapy of metastatic colorectal cancer (mCRC) results in better clinical outcomes.¹

"The RDI of cytotoxic agents affects cancer patients' clinical outcome, especially in the curative setting. Poor data are available in mCRC and with specific regard to the use of the triplet FOLFOXIRI," explain study authors Moretto et al. In response to this gap, therefore, the authors performed a pooled analysis of the phase III TRIBE and TRIBE2 studies comparing FOLFOXIRI/bev to doublets (FOLFOX or FOLFIRI)/bev) in order to assess the prognostic impact of the RDI (<80% vs. ≥80%) during the first eight cycles of induction treatment of both the triplet and the doublet regimens.

According to the authors, 282/581 (49%) and 404/580 (70%) of patients treated with FOLFOXIRI/bev and doublets/bev, respectively, received an RDI of ≥80%. Patients receiving RDI ≥ 80% had more favorable clinical conditions and tumor-related prognostic features, and RDI ≥ 80% was associated with a higher objective response rate (62% vs 53%) and longer progression-free survival (11.5 vs. 10.0 months) and overall survival (27.9 vs. 22.2 months) times. These results were separately confirmed by multivariable modeling.

Separately, similar objective response rates (58% vs. 56%) and progression-free survival (10.8 vs. 10.0 months) and overall survival (22.9 vs. 24.9 months) times were observed between patients treated with FOLFOXIRI/bev receiving RDI < 80% and those treated with doublets/bev receiving RDI ≥ 80%.

Meanwhile, it was also determined that patients in the RDI < 80% group experienced a greater incidence of severe chemo-related adverse events (72% vs. 34%).

"Maintaining an adequate RDI in the first-line therapy of mCRC improves patients' clinical outcomes. Since there is no benefit from chemotherapy intensification in the case of low RDI, the secondary prophylaxis of chemotherapy-related severe adverse events might be preferrable rather than individual agents' dose reductions," conclude the authors.

Reference

1. Moretto R, Rossini D, Polito MG, et al. The relative dose intensity of first-line FOLFOXIRI and FOLFOX/FOLFIRI both in combination with bevacizumab affects prognosis of metastatic colorectal cancer patients: a pooled analysis of TRIBE and TRIBE2 studies. Eur J Cancer. 2025:222:115470.