Palbociclib in metastatic breast cancer: current evidence and real-life data

Abstract

The purpose of this review is to summarize the background and latest evidence for the use of palbociclib, an oral, first-in-class, highly selective cyclin-dependent kinase 4/6 inhibitor, in advanced breast cancer, with a focus on some of the unanswered questions about the performance of this agent in clinical practice. The available clinical data from both controlled clinical trials and real-life experiences concerning palbociclib-based combinations in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic disease, including patient-reported outcomes and subgroup analyses, have been reviewed and discussed. Palbociclib significantly improved progression-free survival and clinical benefit rates when added to letrozole in postmenopausal women as initial endocrine-based therapy, and it prolonged progression-free survival and overall survival when added to fulvestrant in women who progressed on previous endocrine therapy in randomized clinical trials. Tolerability profile was manageable, with neutropenia occurring most commonly, without detrimental impact on quality of life. Available data from real-life experiences confirm the good performance of palbociclib in unselected, heavily pretreated populations. Palbociclib in combination with endocrine therapy is a valuable emerging option for patients with HR+/HER2− advanced or metastatic breast cancer. Further investigation is needed to provide solutions for palbociclib resistance and to identify the best sequence to use for the best patient benefit with a minimal toxicity.

Computational analysis of Cyclin D1 gene SNPs and association with breast cancer

“…Breast cancer is worldwide emerging disorder of women with approximately 2.1 million new cases are diagnosed and almost 0.6 million deaths in each year [ 30 ]. The overall survival rate of patients with breast cancer has reached up to 90%,;however, metastatic or advanced breast cancer survival rate is still 25% [ 31 ]. Recent therapeutic approach which includes endocrine therapy and targeted therapy is productive in prognosis of breast cancer.…”

Complementary Targeting of Rb Phosphorylation and Growth in Cervical Cancer Cell Cultures and a Xenograft Mouse Model by SHetA2 and Palbociclib

“…To complement SHetA2 degradation of cyclin D1, we hypothesized that combination treatment with a CDK 4/6 inhibitor drug could block the activity of any remaining cyclin D1/CDK 4/6 complexes in a synergistic manner (Graphical Abstract). Palbociclib is a CDK 4/6 inhibitor currently used in the treatment of hormone receptor positive-metastatic breast cancers and being evaluated in clinical trials of multiple other cancer types [16]. The combination of these two drugs is predicted to have reduced side effects in comparison to current standard of care treatment for cervical cancer.…”

Palbociclib-Induced Pneumonitis: A Case Report and Review of the Literature

“…Palbociclib is an oral cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor that can be incorporated in addition to endocrine therapy for the treatment of metastatic HR+/ERBB2− breast cancer [ 4 - 6 ]. Palbociclib can be used in the first line of treatment in combination with letrozole, an oral AI, or in a subsequent line in combination with fulvestrant, a selective estrogen receptor degrader [ 3 , 4 ]. Various grade 3 or 4 side effects were noted in the palbociclib-fulvestrant group of the PALOMA3 clinical trial and the palbociclib-letrozole group of the PALOMA-2 clinical trial [ 5 , 6 ].…”