Safety and efficacy of cyclin-dependent kinase inhibitor rechallenge following ribociclib-induced limiting hypertransaminasemia

Abstract

Cyclin-dependent kinase inhibitors (CDKIs) and endocrine therapy (ET) are the corner-stone of systemic therapy for patients with hormone-positive (HR+) HER2-negative metastatic breast cancer (MBC). However, limited data exist regarding rechallenge treatment strategies with CDKIs after limiting toxicity. In this report, we provide evidence of the safety and efficacy of sequential treatment with palbociclib or abemaciclib in 6 HR+/HER- MBC patients who experienced grade ≥3 ribociclib-induced hypertransaminasemia. Until results from large observational or randomized studies are communicated, empirical evidence may help make individualized decisions on CDKI rechallenge beyond ribociclib-induced unacceptable liver toxicity.

Keywords: CDK inhibitors; Hypertransaminasemia; Luminal; Metastatic breast cancer; Rechallenge.

Fig. 1

Time course of serum liver aminotransferases, tumor markers CEA and Ca15.3, and tumor response by RECIST, in the 6 patients exposed to a rechallenge strategy with palbociclib or abemaciclib after ribociclib-induced limiting hypertransaminasemia. The different treatments choices are indicated below. The duration of the CDKI interruptionhormonal partner, and subsequent CDKI, is denoted by black solid lines. The box above shows the extension of the metastatic disease at the time of ribociclib initiation. ALT: alanine aminotransferase. AST: aspartate aminotransferase. CD: cycle and day of CDKI treatment. W: week. Mo: months. PFS: progression-free survival. PR: partial response. MPR: maintained partial response. PD: progressive disease.