Impact of Relative Dose Intensity of Chemotherapy on Clinical Outcomes in Metastatic Colorectal Cancer

Pooled analysis results from the phase 3 TRIBE and TRIBE2 studies suggest that a higher relative dose intensity of first-line FOLFOXIRI or FOLFOX/FOLFIRI plus bevacizumab improves outcomes among patients with metastatic colorectal cancer. 

“The relative dose intensity of cytotoxic agents affects cancer patients’ clinical outcome, especially in the curative setting,” stated Roberto Moretto, MD, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy, and coauthors. “Poor data are available in [metastatic colorectal cancer] and with specific regard to the use of the triplet FOLFOXIRI.” 

In this study, researchers collected data from 1161 patients who received either FOLFOXIRI plus bevacizumab (n = 581), or FOLFOX or FOLFIRI plus bevacizumab (n = 580) at a relative dose intensity of either ≥ 80% (FOLFOXIRI, n = 282; FOLFOX/FOLFIRI, n = 404) or < 80% (FOLFOXIRI, n = 299; FOLFOX/FOLFIRI, n = 176) for the first 8 cycles of the regimens. Primary end points included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). A key secondary end point was safety. 

At analysis, for patients treated with a relative dose intensity of ≥ 80%, ORR was 62% in the FOLFOXIRI arm and 53% in the FOLFOX/FOLFIRI arm (odds ratio [OR] 1.44; 95% confidence interval [CI], 1.13 to 1.82; P = .0026), PFS was 11.5 months in the FOLFOXIRI arm and 10 months in the FOLFOX/FOLFIRI arm (hazard ratio [HR] 0.80; 95% CI, 0.71 to 0.91; P < .001), and OS was 27.9 months and 22.2 months (HR 0.75; 95% CI, 0.65 to 0.85; P < .001), respectively. 

For patients treated with a relative dose intensity of < 80%, the ORR was 58% in the FOLFOXIRI arm and 56% in the FOLFOX/FOLFIRI arm (OR 1.09; 95% CI, 0.81 to 1.48; P = .57), PFS was 10.8 months in the FOLFOXIRI arm and 10 months in the FOLFOX/FOLFIRI arm (HR 0.96; 95% CI, 0.83 to 1.12; P = .63), and OS was 22.9 months and 24.9 months (HR 1.07; 95% CI, 0.90 to 1.26; P = .46), respectively. 

The incidence of severe chemotherapy-related adverse events was 72% in patients treated at a relative dose intensity of < 80% and 34% in patients treated at a relative dose intensity of ≥ 80% (P < .001). 

“Maintaining an adequate [relative dose intensity] in the first-line therapy of mCRC improves patients’ clinical outcomes,” concluded Dr Moretto et al. “Since there is no benefit from chemotherapy intensification in the case of low [relative dose intensity], the secondary prophylaxis of chemotherapy-related severe adverse events might be preferable rather than individual agents’ dose reductions.”

Source: 

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. Published online: April 26, 2025. doi: 10.1016/j.ejca.2025.115470