The Study: We’ve know for quite a while that CDK4/6 inhibition improves progression-free survival (PFS) by leaps and bounds, and now it has finally laid the golden egg of improved overall survival (OS). PALOMA-3 randomized 521 women progressing on first-line endocrine therapy to receive fulvestrant +/- palbociclib. Median OS times were pretty dramatically improved from 28 to 35 months. But given both survival times were relatively long, the hazard ratio fell just short of “significant” with the upper boundary of the confidence interval just a smudge over 1. Pre-specified subset analyses demonstrated those who never proved sensitive to previous endocrine therapy (n=111) and especially pre-menopausal women (n=108) seemed to be the buzzkill. With either of those groups excluded from analyses, even the statisticians were satisfied with a clearcut survival benefit.
Bottom Line: The huge PFS advantage seen with CDK4/6 inhibition eventually translates to a proportional OS benefit, particularly among post-menopausal women and those with previous endocrine sensitivity. | Turner, N Enlg J Med 2018