Background Recent data suggest that BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients with right-sided tumours and ECOG-PS = 0 may achieve benefit from the triplet regimen differently than those with left-sided tumours and ECOG-PS > 0. Methods The predictive impact of primary sidedness and ECOG-PS was evaluated in a large real-life dataset of 296 BRAFV600E-mutated mCRC patients treated with upfront triplet or doublet +/- bevacizumab. Biological differences between right- and left-sided BRAFV600E-mutated CRCs were further investigated in an independent cohort of 1162 samples. Results A significant interaction effect between primary sidedness and treatment intensity was reported in terms of both PFS (p = 0.010) and OS (p = 0.003), with a beneficial effect of the triplet in the right-sided group and a possible detrimental effect in the left-sided. No interaction effect was observed between ECOG-PS and chemo-backbone. In the MSS/pMMR population, a consistent trend for a side-related subgroup effect was observed when FOLFOXIRI +/- bevacizumab was compared to oxaliplatin-based doublets +/- bevacizumab (p = 0.097 and 0.16 for PFS and OS, respectively). Among MSS/pMMR tumours, the BM1 subtype was more prevalent in the right-sided group (p = 0.0019, q = 0.0139). No significant differences were observed according to sidedness in the MSI-H/dMMR population. Conclusions Real-life data support the use of FOLFOXIRI +/- bevacizumab only in BRAFV600E-mutated mCRC patients with right-sided tumours.

Benefit from upfront FOLFOXIRI and bevacizumab in BRAFV600E-mutated metastatic colorectal cancer patients: does primary tumour location matter? / R. Moretto, A. Elliott, D. Rossini, R. Intini, V. Conca, F. Pietrantonio, A. Sartore-Bianchi, C. Antoniotti, C. Rasola, M. Scartozzi, M. Salati, N. Pella, M.A. Calegari, M. Carullo, F. Corti, G. Mauri, M. Fassan, G. Masi, P. Brodskiy, H. Lenz, A. Shields, S. Lonardi, M. Korn, C. Cremolini. - In: BRITISH JOURNAL OF CANCER. - ISSN 1532-1827. - 127:5(2022 Sep 01), pp. 957-967. [10.1038/s41416-022-01852-0]

Benefit from upfront FOLFOXIRI and bevacizumab in BRAFV600E-mutated metastatic colorectal cancer patients: does primary tumour location matter?

F. Pietrantonio;A. Sartore-Bianchi;F. Corti;G. Mauri;
2022

Abstract

Background Recent data suggest that BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients with right-sided tumours and ECOG-PS = 0 may achieve benefit from the triplet regimen differently than those with left-sided tumours and ECOG-PS > 0. Methods The predictive impact of primary sidedness and ECOG-PS was evaluated in a large real-life dataset of 296 BRAFV600E-mutated mCRC patients treated with upfront triplet or doublet +/- bevacizumab. Biological differences between right- and left-sided BRAFV600E-mutated CRCs were further investigated in an independent cohort of 1162 samples. Results A significant interaction effect between primary sidedness and treatment intensity was reported in terms of both PFS (p = 0.010) and OS (p = 0.003), with a beneficial effect of the triplet in the right-sided group and a possible detrimental effect in the left-sided. No interaction effect was observed between ECOG-PS and chemo-backbone. In the MSS/pMMR population, a consistent trend for a side-related subgroup effect was observed when FOLFOXIRI +/- bevacizumab was compared to oxaliplatin-based doublets +/- bevacizumab (p = 0.097 and 0.16 for PFS and OS, respectively). Among MSS/pMMR tumours, the BM1 subtype was more prevalent in the right-sided group (p = 0.0019, q = 0.0139). No significant differences were observed according to sidedness in the MSI-H/dMMR population. Conclusions Real-life data support the use of FOLFOXIRI +/- bevacizumab only in BRAFV600E-mutated mCRC patients with right-sided tumours.
Settore MED/06 - Oncologia Medica
3-giu-2022
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/936247
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