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In the one randomised trial where the four gene-activity subtypes were measured, they predicted not only how long people lived but which biological drug worked better: the immune subtype did better with bevacizumab and the canonical subtype with cetuximab.
The consensus molecular subtypes were characterised with a NanoString gene expression panel on primary tumours from 581 patients enrolled in CALGB/SWOG 80405, a phase 3 trial comparing the addition of bevacizumab or cetuximab to infusional fluorouracil, leucovorin and oxaliplatin or irinotecan as first-line treatment of advanced colorectal cancer. The subtypes were highly prognostic for overall survival (p less than 0.001) and progression-free survival (p less than 0.001), and predictive for both (interaction p less than 0.001 for overall survival and 0.0032 for progression-free survival). In the CMS1 cohort, patients treated with bevacizumab lived significantly longer than those treated with cetuximab (p less than 0.001); in the CMS2 cohort, patients treated with cetuximab lived significantly longer than those treated with bevacizumab (p = 0.0046).
It is the strongest evidence that the consensus subtypes could choose between the two first-line biologicals, and the clearest statement of why they have not: it is a retrospective analysis of a subset of one trial, on an assay nobody has validated for clinical use.
Shares Alan P. Venook, Heinz-Josef Lenz, VEGF / VEGFR, Cetuximab.
Shares Alan P. Venook, Heinz-Josef Lenz, Consensus molecular subtypes (CMS1-4), VEGF / VEGFR.
Shares Heinz-Josef Lenz, Cetuximab, Bevacizumab, EGFR.
Shares VEGF / VEGFR, Bevacizumab, Colorectal cancer.
Shares Consensus molecular subtypes (CMS1-4), RNA sequencing & expression profiling, Colorectal cancer.
Shares VEGF / VEGFR, Cetuximab, Bevacizumab, EGFR.
Shares Cetuximab, Bevacizumab, Colorectal cancer.
Shares VEGF / VEGFR, Cetuximab, Bevacizumab, EGFR.