Good morning. It’s a pleasure for me to present briefly the main results of this MONARCH-3 trial. MONARCH-3 is a trial that has been designed to test the clinical activity of abemaciclib in combination with non-steroidal aromatase inhibitors as an initial therapy for menopausal patients with endocrine sensitive HER2 negative advanced breast cancer. Abemaciclib is a potent CDK4 and 6 inhibitor and we know, since now more than ten years, that the cyclin D1 CDK4/6 pathway plays a key role in promoting proliferation of ER positive breast cancer. So the idea was that combining a CDK4/6 inhibitor such as abemaciclib with endocrine therapy could improve the activity of endocrine therapy alone. Here you can see, indeed, the design of the study, a very simple design – two arms. The experimental arm with abemaciclib in combination with endocrine therapy and the control arm where patients received placebo plus endocrine therapy.
The study recruited 493 patients, all patients were menopausal, they had endocrine sensitive HER2 negative advanced breast cancer. They did not receive any prior treatment for metastatic disease. The primary endpoint of the study was the comparison in terms of progression free survival between the two treatment arms, the experimental arm versus the placebo arm. As you can see, there is a statistically and clinically significant difference in terms of progression free survival between the two arms. The abemaciclib arm is superior to the control arm with a difference that is statistically significant, a hazard ratio of 0.54.
These are the main results in terms of side effects. I will not go into the details of this busy slide, I just want to draw your attention to the fact that using abemaciclib is associated with an increase in the rate of diarrhoea and also an increase in the rate of neutropenia. However, despite the increase in the rate of neutropenia the episodes of neutropenic fever in patients receiving abemaciclib are quite uncommon. Actually we had only one patient who had neutropenic fever and was treated with abemaciclib.
So basically the conclusions of our study are that abemaciclib in combination with a non-steroidal aromatase inhibitor is superior than a non-steroidal aromatase inhibitor alone in terms of progression free survival but also in terms of the objective response rate as the initial treatment of HER2 negative endocrine sensitive advanced breast cancer in postmenopausal patients. The effect of abemaciclib is seen in all the different subgroups, however we have observed that the patients deriving the largest benefit from abemaciclib are those who have adverse prognostic factors such as, for instance, the presence of liver metastases or the fact that the disease has relapsed only after a few years from the end of adjuvant endocrine therapy. While we suggest, I didn’t have the time to show this data to you, but we suggest with the present study that patients with good prognosis such as, for instance, those who have only bone metastases may still be treated with endocrine therapy alone. In terms of side effects you can see, as already mentioned, that there is an increase in neutropenia, an increase in diarrhoea but overall the management of these side effects is absolutely feasible and patients can tolerate the treatment and receive the treatment quite continuously. Thank you very much for your attention.