Targeting the cyclin-dependent kinases 4/6 in advanced breast cancers

The historical median survival of advanced luminal breast cancer does not exceed four years. The deciphering of the mechanisms of resistance to hormone therapy has led to the development of inhibitors of cyclin D dependent kinases (CDK4 and 6). Three drugs, palbociclib, ribociclib and abemaciclib, very similar pharmacologically, have been evaluated in the context of pivotal, randomized phase III trials. Strikingly and regardless of the endocrine therapy backbone, and in both hormone-sensitive and hormone-resistant patients, the addition of a CDK4 / 6 inhibitor doubles progression-free survival with a hazard ratio always around 0.55. The benefit in overall survival begins to be demonstrated. This review presents all published results, as well as the main safety data.