Can CDK 4/6 inhibitors be used in patients with visceral crises? Deviating from conventional teaching

Abstract

Visceral crisis is a situation in which the vital organ function is impaired due to infiltration by cancer cells. It Is of particular importance in the subset of HR+/Her2- metastatic breast cancer.. Current guidelines that recommend cytotoxic chemotherapy for visceral crisis are based on historical data that indicate that chemotherapy has higher response rates than endocrine therapy. These trials included patients with advanced breast cancer who were not selected for the hormonal receptor or Her 2 receptor status. In addition, the comparator had a weak endocrine agent. Objective response rates with endocrine therapy in combination with any of the CDK 4/6 inhibitors in patients with measurable disease range from 50-59%. These response rates are higher than the chemotherapy rates found in the historical trials. Moreover, patients with visceral crisis have a compromised performance status and impaired organ functions. Therefore, it is unlikely that these patients would tolerate complete doses of the most active chemotherapeutic agents, including anthracycline and taxane. The retrospective analysis of the real-world data base clearly demonstrates that the combination of endocrine agents with a CDK 4/6 inhibitor is superior to chemotherapy with improvement in overall survival. In conclusion, it is time to redefine the guidelines and consider endocrine therapy with a CDK 4/6 combination as the preferred option in the initial management of the visceral crisis.