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Two European randomised trials, analysed separately, each showed the same thing: cetuximab helps left-sided bowel cancers with no RAS mutation and adds little on the right.
Patients with RAS wild-type metastatic colorectal cancer from the CRYSTAL and FIRE-3 trials were classified as left-sided (splenic flexure, descending colon, sigmoid colon or rectum) or right-sided (appendix, caecum, ascending colon, hepatic flexure or transverse colon). In both trials, patients with left-sided tumours (142 and 157) had markedly superior progression-free survival, overall survival and objective response rates compared with right-sided tumours (33 and 38). Among patients with left-sided tumours, FOLFIRI plus cetuximab significantly improved overall survival against the respective comparators, FOLFIRI in CRYSTAL and FOLFIRI plus bevacizumab in FIRE-3; in right-sided tumours the benefit of adding cetuximab was limited in CRYSTAL and outcomes were comparable between arms in FIRE-3. A significant interaction between primary tumour location and treatment was observed for overall survival in both studies (CRYSTAL hazard ratio 1.95; FIRE-3 hazard ratio 0.40) in multivariable models that included sex, prior adjuvant therapy and BRAF status.
It showed the sidedness effect is not an artefact of pooling and survives adjustment for BRAF, which is what made guideline committees act on it.
Shares Volker Heinemann, CRYSTAL & FIRE-3, Sidedness (left vs right colon), Cetuximab.
Shares Volker Heinemann, Heinz-Josef Lenz, CRYSTAL & FIRE-3, Wild-type (WT).
Shares Sidedness (left vs right colon), BRAF, Cetuximab, EGFR.
Shares CRYSTAL & FIRE-3, Sidedness (left vs right colon), Cetuximab, Bevacizumab.
Shares Wild-type (WT), Sidedness (left vs right colon), EGFR, KRAS.
Shares CRYSTAL & FIRE-3, Eric Van Cutsem, Sidedness (left vs right colon), Cetuximab.
Shares Heinz-Josef Lenz, Sidedness (left vs right colon), Cetuximab, Bevacizumab.
Shares CRYSTAL & FIRE-3, Sidedness (left vs right colon), BRAF, Cetuximab.