The L96 6.0 in my 2015 Chevy 2500HD, I find that using E85 I get much better overall experience with hauling, towing, etc. Fuel mileage does indeed tank considerably by using E85, but compared to mid grade and especially premium fuel cost, the actual cost per mile by using E85 is still far less than using those other fuels, and equitable compared to regular.
GM engines, the ECM monitors knock events and adjusts timing accordingly. E85 has 100 octane and allows the ECM to advance timing to max in the ECM map. Driving experience is much better. I could get the same result using premium, but the actual cost per mile would be higher.
As has been stated, higher octane will not deliver better mpg, but it can under some circumstances bring about better overall performance efficiency.
A pickup with a trailer is an aerodynamic nightmare that is going to be a real belly drop when it comes to mpg. A more moderate speed, gradual slowing instead racing full bore and then applying a ton of braking, and other little techniques will go a lot further to improving mpg. Many commercial fleet studies show that the driver alone accounts for 33% of improvement or degradation of fuel economy.