A randomized, open-label, phase IV study evaluating palbociclib plus endocrine treatment versus a chemotherapy-based treatment in patients with hormone receptor-positive, HER2-negative metastatic breast cancer (PADMA)

Background:

Although endocrine therapy (ET) is recommended as first-line therapy for hormone receptor(HR)+/HER2-metastatic breast cancer (MBC), up to 50% of patients receive chemotherapy. Meanwhile new targeted treatments have been developed and the CDK4/6 inhibitor palbociclib improves progression free survival (PFS) of ET alone by about 50%. So far, there is no data comparing chemotherapy with or without maintenance ET and ET in combination with palbociclib as first-line therapy. Clinical trials are often criticized not to mirror the general breast cancer population and every-day clinical practice.

Methods:

PADMA is a low intervention trial with no rigid inclusion and exclusion criteria. Patients with first-line HR+/HER2-MBC who are candidate for mono-chemotherapy will be randomized 1:1 to receive palbociclib plus ET or mono-chemotherapy per investigator's choice +/-maintenance ET. Primary objective is to compare the time-to-treatment-failure, defined as time from randomization to discontinuation of treatment due to disease progression, treatment toxicity, patient's preference, or death. Main secondary objectives are PFS, overall survival at 36 months, toxicity and compliance and patient reported outcome. Data regarding activity levels, patient well-being, quality of life and health care utilization are collected via mobile devices.

Results:

360 patients will be accrued to show an improved time-to-treatment-failure for palbociclib in combination with ET. Recruitment has started in QI/2018 and is planned in 130 sites in Europe and Canada.

Conclusions:

The aim of PADMA is to demonstrate in a real world setting that ET plus palbociclib is superior to a chemotherapy-based strategy as first-line therapy.