Triple double.

Top Line: When it comes to first-line chemo for metastatic colon cancer, a major point of debate is the use of doublet or triplet cytotoxic chemo, either with bevacizumab.

The Study: In the original TRIBE study, triplet chemo (FOLFOXIRI+B) had better progression-free and overall survival than doublet chemo (FOLFIRI+B). However, it’s more toxic, and some wonder if exposure to all three agents (FOLF, OX, and IRI) in sequence (FOLFOX → FOLFIRI) rather than in combo is still effective but less toxic and more feasible. So TRIBE2 compares first-line FOLFOXIRI+B with planned second-line (i.e., reintroduction of) FOLFOXIRI+B versus first-line mFOLFOX6+B with planned second-line FOLFIRI+B. Note this is a preliminary manuscript that hasn’t completed peer review. The primary endpoint of overall time to second progression was statistically longer with triplet therapy (16 → 19 months). Overall survival was also longer (23 → 27 months). That appeared to be driven largely by improvement in first progression-free survival, which was longer with combo-triplet therapy (10 → 12 months), with no difference in time from first to second progression (6 months). This is all despite the facts toxicity was higher with the triplet regimen, and fewer triplet patients went on to receive reintroduction to triplet therapy.

TBL: Upfront exposure to three cytotoxic agents in combo (FOLFOXIRI+B) achieves longer overall survival than exposure to the same three cytotoxic agents in sequence. | Cremolini, Lancet Oncol 2020