Proton pump inhibitors decrease efficacy of palbociclib in patients with metastatic breast.

Area of Science:

• Oncology
• Pharmacology

Background:

• Hormone receptor-positive and HER2-negative metastatic breast cancer (mBC) is a significant clinical challenge.
• Palbociclib is a key therapy, but its efficacy may be influenced by concurrent medications.
• Proton pump inhibitors (PPIs) are commonly used for gastrointestinal protection.

Purpose of the Study:

• To evaluate the impact of concurrent proton pump inhibitors (PPIs) on progression-free survival (PFS) in patients with hormone receptor-positive, HER2-negative metastatic breast cancer (mBC) treated with palbociclib.
• To compare PFS between patients receiving palbociclib with and without concurrent PPIs in first-line and subsequent treatment settings.

Main Methods:

• A retrospective observational study included 165 patients with ER+, HER2- mBC eligible for palbociclib.
• Patients were classified based on PPI use: concurrent (≥2/3 of palbociclib duration) or no concurrent PPIs.
• Progression-free survival (PFS) was analyzed between the two groups.

Main Results:

• In the first-line setting, concurrent PPI use was associated with significantly shorter PFS (8.88 months) compared to no PPI use (67.81 months) (p < 0.0001).
• In second-line or subsequent settings, patients with concurrent PPIs had a PFS of 7.46 months versus 17.29 months without PPIs (p = 0.122).
• A notable negative impact of PPIs on PFS was observed, particularly in the first-line treatment of mBC with palbociclib.

Conclusions:

• Concurrent PPI use negatively impacts PFS in mBC patients treated with palbociclib, especially in the first-line setting.
• The findings suggest a potential drug-drug interaction affecting palbociclib efficacy.
• Further research is warranted to elucidate the mechanisms and clinical implications of PPIs on CDK4/6 inhibitors.