The PALOMA-3 clinical trial investigated a new treatment approach for breast cancer. Its findings have reshaped how certain types of breast cancer are managed, leading to changes in clinical practice.
Understanding Palbociclib
Palbociclib, marketed as Ibrance, is a targeted therapy. It functions as a cyclin-dependent kinase (CDK) 4/6 inhibitor. In cancer cells, CDK4 and CDK6 become overactive, driving uncontrolled cell division.
By inhibiting these kinases, palbociclib prevents the phosphorylation of the retinoblastoma protein (Rb), a key regulator of cell division. This halts the cell cycle in the G1 phase, preventing cancer cells from multiplying. Palbociclib is frequently used with hormone therapy, as this dual approach targets different pathways that contribute to cancer cell survival and proliferation.
The PALOMA-3 Clinical Trial
The PALOMA-3 trial was a Phase 3, randomized, double-blind, placebo-controlled study evaluating palbociclib’s effectiveness. It enrolled 521 premenopausal and postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. All participants had experienced disease progression after receiving prior endocrine therapy.
Patients were randomly assigned in a 2:1 ratio to receive either palbociclib in combination with fulvestrant or a placebo along with fulvestrant. The primary goal of the study was to assess progression-free survival (PFS). Secondary objectives included evaluating overall survival (OS) and safety profiles.
Key Findings and Their Impact
The PALOMA-3 trial demonstrated a significant improvement in progression-free survival (PFS) with the addition of palbociclib. Patients receiving palbociclib plus fulvestrant experienced a median PFS of 9.5 to 11.2 months, compared to 4.6 months for those on placebo plus fulvestrant. This represented a substantial increase in the time patients lived without their disease progressing.
Updated exploratory analyses with over 6 years of follow-up showed improved overall survival (OS). The median OS for the palbociclib group was 34.8 months, compared to 28.0 months in the placebo group, showing a difference of 6.8 months. These results led to regulatory approvals for palbociclib, establishing it as a new standard of care for this subtype of advanced breast cancer.
Who Benefits from This Treatment
Palbociclib is indicated for individuals with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. This treatment is administered in combination with an aromatase inhibitor or fulvestrant, especially after the disease has progressed following prior endocrine therapy. The benefit of palbociclib plus fulvestrant has been observed across most patient subgroups, including those with endocrine-sensitive disease and those who had not received prior chemotherapy for advanced disease.
Managing Treatment and Side Effects
Palbociclib is taken orally, as a 125 mg dose once daily for 21 consecutive days, followed by a 7-day break, completing a 28-day cycle. The most common side effect is neutropenia, a reduction in white blood cell count, which occurred in 83% of patients in PALOMA-3, with 55% experiencing Grade 3 neutropenia and 11% experiencing Grade 4.
Other common side effects include fatigue, nausea, infections, stomatitis (sore mouth), diarrhea, and hair thinning. Regular blood tests are necessary to monitor blood counts, and dose adjustments or temporary interruptions of treatment may be required if neutropenia or other side effects become severe. Patients are encouraged to communicate any new or worsening symptoms to their healthcare team.