@justanotherpt, You've hit on a very important question that impacts all of us that are taking targeted therapies. The dose levels of these medications are primarily determined during phase 1 of the clinical trials. The US FDA's structure of the clinical trial cycle hasn't allowed for flexibility in dosing at later stages of that cycle. For drugs that are further along in the development cycle, going back to stage 1 to adjust the standard recommended dosing can be like starting over. Frankly, we don't have that kind of time. The research needs to stay ahead of any impending drug resistance. There is a program coming from the FDA that should help with balancing side-effects and overall effectiveness from the beginning of the process.
Here's a link to more info on the US FDA's Project Optimus: https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus
"The goal of Project Optimus is to educate, innovate, and collaborate with companies, academia, professional societies, international regulatory authorities, and patients to move forward with a dose-finding and dose optimization paradigm across oncology that emphasizes selection of a dose or doses that maximizes not only the efficacy of a drug but the safety and tolerability as well."