Kefah Mokbel, Chair of Breast Cancer Surgery at London Breast Institute and Honorary Professor of Medicine at Cardiff University School of Medicine, shared a post on LinkedIn:
“Not all CDK4/6 inhibitors are the same
The PALLAS trial failed while monarchE and NATALEE succeeded due to several critical differences: PALLAS used palbociclib with poor treatment completion (only 38% finished 2 years), enrolled a broader, lower-risk population that may not have needed intensive therapy, and crucially, created a post-recurrence treatment disadvantage—only 41% of patients who recurred after adjuvant palbociclib received CDK4/6 inhibitors in the metastatic setting versus 66% in the endocrine therapy-alone arm, essentially negating any adjuvant benefit. In contrast, monarchE used abemaciclib with its unique continuous dosing schedule and additional kinase activities in a highly selected high-risk population (≥4 positive nodes or 1-3 nodes plus high-risk features), while NATALEE compensated for ribociclib’s intermittent schedule with a longer 3-year duration and better tolerability through dose reduction.
The key lesson is that not all CDK4/6 inhibitors are equivalent in the adjuvant setting—success requires the right drug (with adequate potency and schedule), the right patients (sufficient risk to benefit), adequate treatment duration and compliance, and consideration of the entire treatment continuum including whether using a CDK4/6 inhibitor adjuvantly will preclude its effective use at recurrence.
It should be noted that there were more visceral metastasis in the Palbociclib arm!”
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