Addressing physician barriers to administering cyclin-dependent kinases 4 and 6 inhibitors in first-line treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

• Published in: Cancer management and research 2019-01, Vol.11, p.513-524
• Main Authors: Mahtani, Reshma L, Vogel, Charles L
• Format: Article
• Language: English
• Subjects: abemaciclib; Anemia; aromatase inhibitor; Biomarkers; Breast cancer; Cancer therapies; Chemotherapy; Clinical trials; Cyclin-dependent kinases; Endocrine therapy; Epidermal growth factor; Gene expression; Medical research; Metastasis; Neutropenia; Neutrophils; Oncology; palbociclib; Patients; Review; ribociclib; Targeted cancer therapy; Womens health
• ISSN: 1179-1322; 1179-1322
• DOI: 10.2147/CMAR.S186658

Combination therapy with a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor and an aromatase inhibitor (AI) for first-line treatment of postmenopausal women with advanced breast cancer (ABC) has demonstrated improvement in progression-free survival (PFS) over AI monotherapy without adding substantial toxicity. However, CDK4/6 inhibitor plus AI therapy is not uniformly used as first-line therapy for ABC, indicating that barriers to CDK4/6 inhibitor use exist. Such barriers may include the following perceptions: patients with bone-only metastases, with a long disease-free interval, or who are older may respond to AI monotherapy and may not benefit from a CDK4/6 inhibitor; tumor response rates may be lower and delayed with CDK4/6 inhibitor plus AI therapy than chemotherapy; the increased incidence of adverse events with CDK4/6 inhibitor plus AI therapy outweighs benefits; and the cost of CDK4/6 inhibitors may be prohibitive. Some of these barriers are addressed with data from follow-up analyses of CDK4/6 inhibitor trials, which have shown a PFS benefit of combination therapy in all subgroups assessed, including older patients, those with bone-only metastatic disease, and those with a long disease-free interval. Tumor response rates with CDK4/6 inhibitor plus AI therapy are comparable to those with first-line cytotoxic chemotherapy. Finally, adverse events associated with CDK4/6 inhibitor plus AI therapy are manageable and occur with decreasing severity during treatment, with similar reports of quality of life to those with AI monotherapy. These data support CDK4/6 inhibitor plus AI therapy as the standard of care in first-line treatment of ABC.