CDK4/6 inhibitors as a treatment for advanced breast cancer

CDK4/6 inhibitors are a relatively new class of drugs often used for advanced metastatic breast cancer in combination with anti-hormonal therapy to complement standard treatment. In Switzerland, health insurers provide coverage for the three inhibitors CDK4/6 palbociclib, ribociclib and abemaciclib. New studies indicate that not all CDK4/6 inhibitors contribute equally to prolonging survival of breast cancer patients or to improving their quality of life. Moreover, the studies report strong side effects. The aim of this report is to compare the efficacy, cost-effectiveness and safety of each of these three drugs when they are combined with the standard therapy, not only with each other but also with the standard therapy on its own. It will also consider any ethical and organisational aspects involved.

The selected studies compared the combination therapies that consist of a standard therapy plus one of these three drugs with the standard therapy without additional interventions. The authors made indirect comparisons using modelling to compensate for the lack of comparative studies on the combination therapies. The comparisons show that using CDK4/6 inhibitors probably has a positive effect on the healing process; however, the standard therapy alone is better tolerated. The combination therapy, comprising of CDK4/6 inhibitors and the standard therapy also requires more medical care to monitor the side effects. A comparison of the three CDK4/6 inhibitors’ respective efficacy yielded no clear results. However, there were differences in terms of cost-benefit ratio between the three drugs. In patients with resistance to anti-hormonal therapy, the combination therapy with ribociclib had the best cost-benefit ratio. In these cases, not using abemaciclib would save costs. In women without resistance, the cost-benefit effect was greater with abemaciclib. Refraining from using palbociclib would save costs in this instance.

The report concludes that the combination therapies consisting of CDK4/6 inhibitors and standard therapy can increase efficacy but will increase the need for medical care and produce more side effects. Differences in the cost-benefit ratio result from the specific combination used, which in turn depends on whether a resistance is present. Further studies are ongoing and might produce more detailed results in future.