A novel analysis of data from the PALOMA-3 trial confirms the efficacy of palbociclib and provides an option for efficacy assessments that could accelerate drug approvals.

Abstract

1069 Background: Advances in breast cancer (BC) therapy the past few decades have led to higher survival rates. Beginning with palbociclib, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have emerged as a treatment option for BC. We analyzed data from PALOMA 3 that could release a biomarker of OS in patients that receive palbociclib. Methods: We estimated concurrent rates of growth ( g) and regression ( d) from the 393 women with advanced BC enrolled in PALOMA-3 who had radiographic tumor measurement data including 261 treated with fulvestrant + palbociclib, and 132 with fulvestrant + placebo. We analyzed data using a model defined as SLD (t) = exp (– d x t) + exp ( g x t) – 1, where SLD = sum of longest diameters and t = time. We examined the relationship between g and overall survival (OS) and compared the median growth rates ( g) of various cohorts. Results: g values associate highly with OS (p<0.0001). Emulating results in the clinical trial, palbociclib slowed the median g values of the entire population and those with sensitivity to previous endocrine therapy but not those deemed resistant. Further cohort analyses found greater benefit with palbociclib in those with visceral metastases, and longer disease-free interval, and benefit independent of ECOG PS, menopausal status, prior lines of therapy, and age. With only the baseline and two additional scans obtained, the median g values of the palbociclib and placebo arms were statistically different: p=0.038 after 28 (19/9) patients and p=0.0043 after 40 (26/14) patients. Conclusions: Estimates of palbociclib’s impact on tumor growth rates ( g) confirm its efficacy in PALOMA 3. Our ability to discern differences in g, a value associated with OS, after only two follow up scans in as few as 28 patients merits considering g an early biomarker of OS benefit that could bring effective drugs to patients as rapidly as possible. [Table: see text]