CDK-4/6 inhibitors for the treatment of HR+/HER2 – advanced/metastatic breast cancer
CDK-4/6 inhibitors for the treatment of HR+/HER2
The combination of cyclin dependent kinase 4/6 inhibitors with endocrine therapy is the standard therapy in hormone receptor positive HER-2 negative metastatic breast cancer (HR+/HER2− MBC). Several randomized trials have shown the benefits of this combination.
Hormone receptor positive human epidermal growth factor 2 negative (HR+/HER2−) subtype is very common and for over a decade, hormonal therapies were the initial treatment of choice for metastatic breast cancer patients with this subtype1, even though it still remains very challenging to treat. However, endocrine resistance has marred the success rates of this treatment strategy. This has in turn led to finding out newer inhibitors for this heterogeneous group of cancers.
Hormone receptor positive human epidermal growth factor 2 negative (HR+/HER2−) subtype is very common and for over a decade, hormonal therapies were the initial treatment of choice for metastatic breast cancer patients with this subtype1, even though it still remains very challenging to treat. However, endocrine resistance has marred the success rates of this treatment strategy. This has in turn led to finding out newer inhibitors for this heterogeneous group of cancers.
The US food and Drug Administration (FDA) approved the use of three cyclin dependent kinase (CDK) inhibitors (palbociclib, ribociclib & abemaciclib) for the treatment of HR+/HER2− locally advanced or metastatic breast cancer. The use of a selective cyclin dependent kinase (CDK) 4/6 inhibitor, Palbociclib in combination with an aromatase inhibitor as initial endocrine therapy or Fulvestrant following endocrine therapy has been approved in HR+/HER2− patients with advanced/metastatic breast cancer. The placebo controlled PALOMA-2 study showed a higher median progression free survival (PFS) for patients treated with Palbociclib and Letrozole (27.6 months) as compared to those with placebo and Letrozole (14.5 months). Thereafter, in the PALOMA-3 trial, patients with relapsed/ refractory HR+/HER2− advanced/ metastatic breast cancer, a higher PFS was noted in patients receiving Palbociclib and Fulvestrant (9.5 months) in comparison to those receiving Placebo and Fulvestrant (4.6 months). These favorable findings have established the use of Palbociclib in HR+/HER2- advanced or metastatic breast cancer.
