How do you view the use of adjuvant CDK4/6 inhibitors overall given discordant results between MonarchE and PALLAS?  

Given the final results of PALLAS (SABCS 2021), there is no role for adjuvant palbociclib in high risk ER positive breast cancer at this time. No subgroup seemed to benefit. We await the extensive translational studies to get a better idea of what went on with the trial. 45% of patients discontinued...

Many of us suspect that the key difference might be the constant suppression of cell growth by 3 on 1 off vs 4 constant exposure to the CDK4/6 inhibitor. In this adjuvant setting, more likely than not, we are dealing with minimal residual disease. So while 3 on 1 off might be sufficient to induce th...

The clinical characteristics of the patients differ. MonarchE included higher risk patients, thus greater benefit was seen. In the metastatic setting, all 3 CDK 4/6 inhibitors are similarly active, suggesting a class effect. However, abemaciclib does differ in that it is given continuously.

The NeoPal study was also a negative study showing no benefit of Palbo+Let for neoadjuvant disease. Rb phosphorylation rebounds when CDK4/6 treatment is interrupted. The NATALEE trial is also different in the amount of drug given and the duration so I don't think these trials can be compared as pati...