How do you manage ALK-inhibitor AEs which are low grade but significantly impact patient QOL over time?  

How to manage ALK directed therapy adverse events that are low-grade but significantly impair quality of life remains a challenge. Some of these adverse events include fatigue, nausea, rash, and loss of appetite. More often than not, these side effects are not pronounced but over time can impair qua...

Really have not come across this issue that a low grade AE has impacted QOL. I usually consider a short break of 2-4 days first. In many patients, symptoms improve and can resume the drug at the same dose. If symptoms don't improve, consider reducing the dose. 

If the toxicities are sufficiently affecting patient's QOL, I recommend a brief drug holiday followed by consideration of dose reduction. Many of the doses utilized are based on MTD in phase I studies which can exceed the threshold for biological efficacy. For example, alectinib is approved in the U...

Dose reductions are very useful in this setting and are associated with preserved efficacy.