I think this is an extremely important question with broad applicability to drug dosing in general, and particularly in the elderly who not uncommonly are both less tolerant and less forgiving of side effects. If drug efficacy is truly maintained over a range of dosing and not just dose related rela...

This is an intriguing question, again lacking data- whether a ramp up could be possible to avoid toxicity. Dose reductions in all the CDK 4/6 i trials were built in, and efficacy remains. 2 years is too long to tolerate significant toxicity, so dose reductions are clearly necessary and indicated in ...

In the setting of metastatic disease, the dose reduction based on tolerance depends on the size of the smallest pill available. For metastatic disease, in patients where we are concerned about side effects, we will often start at a lower dose and work up to their best dose. In the adjuvant sett...

Actually, there is data on dose reduction and continued efficacy in MONARCH 2. The recommendations are to dose reduce 50mg bid until you reach 50mg bid dose and if not tolerated, discontinue. Efficacy appears to be sustained through the reductions. 

All of the data demonstrate that diarrhea, particularly grade 2-3 diarrhea, is much more common during the first few weeks of treatment with abemaciclib; after that, the incidence of higher grades of diarrhea is much lower. While some of this improvement may be attributed to identifying patients who...