CDK4/6 inhibitors in breast cancer: differences in toxicity profiles and impact on agent choice. A systematic review and meta-analysis.

INTRODUCTION CDK4/6 inhibitor approval for hormone-responsive breast tumours has significantly changed therapeutic algorithms, with three drugs currently approved. AREAS COVERED Here, we analyse the toxicity profiles of palbociclib, ribociclib and abemaciclib through a systematic review and meta-analysis. Palbociclib and ribociclib showed high rates of haematological toxicity, primarily neutropenia, and were associated with a low rate of severe infections. Abemaciclib was associated with a high rate of gastrointestinal toxicities, primarily diarrhoea, of grade 1-2 in most cases. Ribociclib was associated with a high rate of hepatic, and respiratory toxicity and with QTc prolongation. The toxicity rate of ribociclib was higher in metastatic patients than non-metastatic patients, with approximately 33% more grade 3-4 toxicities and 21% more grade 3-4 neutropenic events. A 5% higher risk of diarrhoea was observed in postmenopausal patients. Pre-treated patients did not show a higher toxicity rate for palbociclib/ribociclib than previously untreated patients, while a 26% higher risk of any grade neutropenia and 6% higher risk of grade 3-4 diarrhoea were observed with abemaciclib. The small sample size is the major limitation to the subgroup analysis. EXPERT OPINION Considering the similar efficacies and indications of palbociclib, ribociclib and abemaciclib, the evaluation of their toxicity profiles may facilitate treatment choice.