Palbociclib added to the Pharmaceutical Benefits Scheme

Palbociclib has recently listed on the Pharmaceutical Benefits Scheme (PBS) for the treatment of locally advanced or metastatic breast cancer. Palbociclib is a selective inhibitor of cyclin-dependent kinases (CDKs) 4 and 6. Cyclins and their complex interactions with associated kinases are important drivers of the mammalian cell cycle. Dysregulation of these processes frequently occurs in breast cancer, leading to uncontrolled cellular proliferation.

The double-blind, phase 3 PALOMA-2 study investigated the efficacy of palbociclib with letrozole compared to placebo plus letrozole. The progression-free survival (PFS) was 24.8 months in the palbociclib-letrozole group compared to 14.5 months in the placebo-letrozole group. Follow-up is ongoing to allow assessment of overall survival. The rate of Grade 3-4 adverse events was higher in the palbociclib-letrozole group, with 9.7% of patients permanently discontinuing treatment (compared to 5.9% in the placebo-letrozole group). The most common Grade 3 and 4 events reported in the palbociclib-letrozole group were neutropenia and leukopenia at 66.4% and 24.7% respectively, compared to 1.4% and 0% for the placebo-letrozole group.

Palbociclib is the second cyclin-dependent kinase (CDK) inhibitor to be listed for breast cancer following the approval of ribociclib in July 2018. The PBS conditions for palbociclib are similar to those of ribociclib in that the condition must be hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative and treatment must be in combination with anastrozole or letrozole. Studies suggest that palbociclib has similar efficacy to ribociclib in terms of PFS delay, overall response rate, and time to deterioration in quality of life. Their spectrum of adverse effects is also similar, although palbociclib does not appear to prolong the QTc interval.