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Testing the triplet as a whole strategy rather than one line of treatment. Using all three drugs first, and again after progression, worked better than saving them.
TRIBE2 randomised 679 patients with unresectable, previously untreated metastatic colorectal cancer to upfront FOLFOXIRI plus bevacizumab with reintroduction of the same regimen after progression, or to mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab. The primary endpoint, progression-free survival 2 (time to progression on any second-line treatment), was 19.2 against 16.4 months (hazard ratio 0.74, 95% CI 0.63 to 0.88, p=0.0005). Grade 3 or 4 diarrhoea (17 against 5 percent) and neutropenia (50 against 21 percent) were more common with the triplet during first-line treatment, and eight treatment-related deaths occurred in the experimental group against four in the control group. The trial answered the objection to TRIBE, that the triplet merely front-loads drugs that would have been used anyway.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
Shares TRIBE, FOLFOXIRI (5-FU, leucovorin, oxaliplatin, irinotecan), FOLFIRI (5-FU, leucovorin, irinotecan), VEGF / VEGFR.
Shares VEGF / VEGFR, Anti-angiogenic therapy, Bevacizumab, Cytotoxic chemotherapy.
Shares FOLFIRI (5-FU, leucovorin, irinotecan), FOLFOX (5-FU, leucovorin, oxaliplatin), Anti-angiogenic therapy, Bevacizumab.
Shares FOLFIRI (5-FU, leucovorin, irinotecan), Anti-angiogenic therapy, Bevacizumab, Cytotoxic chemotherapy.
Shares FOLFIRI (5-FU, leucovorin, irinotecan), Anti-angiogenic therapy, Bevacizumab, Colorectal cancer.
Shares FOLFIRI (5-FU, leucovorin, irinotecan), VEGF / VEGFR, FOLFOX (5-FU, leucovorin, oxaliplatin), Anti-angiogenic therapy.
Shares FOLFOXIRI (5-FU, leucovorin, oxaliplatin, irinotecan), FOLFIRI (5-FU, leucovorin, irinotecan), FOLFOX (5-FU, leucovorin, oxaliplatin), Cytotoxic chemotherapy.
Shares FOLFOXIRI (5-FU, leucovorin, oxaliplatin, irinotecan), FOLFIRI (5-FU, leucovorin, irinotecan), FOLFOX (5-FU, leucovorin, oxaliplatin), Cytotoxic chemotherapy.