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.