Doublet, doublet, toil and troublet.

Standard treatment for metastatic colon cancer (that’s not MSI-high) is a 5FU doublet (typically with oxaliplatin) +/- irinotecan +/- an antiangiogenic agent. But have you ever noticed the guidelines don’t provide an expiration date? Meaning these patients stay on a pretty toxic combo of treatments indefinitely. Thus the phase 2 MACBETH trial was born. It enrolled 116 patients with KRAS wild type metastatic colon cancer who all got mFOLFOXIRI + cetuximab for a max of 8 cycles (over 4 months) and then were randomized to maintenance cetuximab versus bevacizumab monotherapy with none continuing chemo. The design was quite ambitious: the authors hoped this less intensive maintenance would improve the rate of progression-free survival at 10 months from the historical 50% with ongoing combo chemo to 70% with mono-targeted therapy. Well, it didn’t. The rates were 50% with maintenance cetuximab and 40% with bev. TBL: A 5FU doublet chemo regimen in combo with an antiangiogenic agent remains the standard treatment for non-MSI-H, KRAS wildtype metastatic colon cancer, well, indefinitely. | Cremolini, JAMA Oncol 2018