In-ear headsets are always going to be better, even without ANR.
The catch is that one needs custom-moulded earplugs, and the usage needs to eliminate tugging on the cable(s) otherwise the plug gets pulled out a little and suddenly a lot of noise gets in. I bought the Mach 1 in-ear headset (not cheap) and while it worked very well, it was very sensitive to cable movement, and after I while I went back to the Bose and flogged the M1 on U.S. Ebay.
For extreme applications, one can use a headset together with earplugs, and turn the headset power way up to compensate. This is OK with cheap headsets but not so good with the Bose whose max volume is limited.
I've done flights over 7hrs with the Bose and had no discomfort whatsoever.