Good morning. On behalf of my co-investigators I’d like to thank ASCO for inviting us to present our results here at this press briefing this morning.
By way of background let’s look at the scope of breast cancer – how big is this problem? In 2019 over 268,000 women will be diagnosed with breast cancer and approximately 20% of these diagnoses will be in women under the age of 50. Breast cancer is the leading cause of cancer deaths in women under the age of 45 years and at least two-thirds of breast cancers are hormone receptor positive, so they are fuelled by or driven by the female hormone oestrogen. Compared with older women, younger women with breast cancer tend to have poorer prognoses and more aggressive behaving disease biology, even when it’s hormone receptor positive, yet premenopausal patients are under-represented in clinical trials.
Ribociclib is a CDK4/6 inhibitor which is approved for advanced HER2 negative, hormone receptor positive breast cancer. It’s approved as initial therapy in combination with an aromatase inhibitor in pre-, peri- and postmenopausal patients based on the results of a group of studies called the MONALEESA trials. These studies showed a significant improvement in progression free survival such that women treated in this first line setting have a median progression free survival of roughly two years which is 10-12 months longer than patients treated with endocrine therapy alone. So these drugs are extending the length of time women can live without their disease progressing. It’s also approved in combination with fulvestrant in postmenopausal women with advanced hormone receptor positive breast cancer as initial endocrine therapy or after disease progression.
We are today going to be presenting overall survival results from one of these MONALEESA trials, the MONALESSA-7. It’s important to note that it’s very difficult in metastatic breast cancer studies to demonstrate a significant improvement in overall survival because patients have the opportunity to receive subsequent treatments after coming off trial, many times multiple lines of therapy, and can even in the situation where a therapy is FDA approved, such as ribociclib, cross over to receive therapy after coming off trial.
MONALEESA-7 is the first study to evaluate a CDK4/6 inhibitor exclusively in younger premenopausal women. This is the design of the MONALEESA-7 study, it’s designed for pre- and perimenopausal women under the age of 59 years with hormone receptor positive advanced breast cancer. They were not allowed to have received prior endocrine therapy for advanced disease but they could have received up to one prior line of chemotherapy for metastatic disease though only a minority of those patients did so, fewer than 15%. 672 women were randomly assigned 50:50 to receive ribociclib with this dosing, three weeks on, one week off, plus a non-steroidal aromatase inhibitor or tamoxifen, the patients and physicians got to choose which the patient would go on. Then all patients received goserelin to turn off their ovaries’ production of oestrogen. The other arm was placebo with this endocrine therapy.
Now, we published in 2018 in Lancet Oncology the primary endpoint of progression free survival and demonstrated that women in the ribociclib arm had a median PFS of 23.8 months, which was 10 months better than patients in the placebo arm. What we are presenting today is the key secondary endpoint of overall survival. These are the overall survival data shown here with a median duration of follow-up at this interim analysis of almost 35 months which was an additional 15 months from the primary analysis. There were 35 patients in the ribociclib arm who are still receiving study treatment at the time of data cut-off and we demonstrated an approximate 29% relative reduction in the risk of death with this treatment, ribociclib.
I’d like to look here at this landmark analysis at the bottom. What we did is we took a look at 42 months here to see the percentage of patients alive at 42 months in each of the arms. In the placebo arm 46% of patients were alive at 42 months and that compares to 70.2% of patients in the ribociclib arm.
Now, as I mentioned at the study design slide, patients had a choice between receiving an aromatase inhibitor or tamoxifen. The vast majority of patients, 495, actually received an aromatase inhibitor so let’s focus on the curve on the left. What you can see is that the hazard ratio and the landmark analysis and the median overall survival were all similar to what I just showed you for the overall population. On the right is the smaller subgroup who received tamoxifen and I would just like to point out here that this is a smaller subgroup. We actually do not give tamoxifen with ribociclib; subsequent to this study closing it was determined that tamoxifen is associated with a prolongation of the QT interval so it could put patients at risk for arrhythmia so it is not approved in combination with tamoxifen.
In conclusion, ribociclib plus endocrine therapy resulted in a statistically significant longer overall survival compared with endocrine therapy alone. As of the data cut-off 35% of patients in the ribociclib arm were still receiving treatment which was higher than the patients on placebo. Patients who received an aromatase inhibitor demonstrated a similar overall survival benefit compared to the overall population and the safety remained consistent with the known tolerability profile which we published again in 2018. This is the first time a statistically significant improvement in overall survival has been observed with a CDK4/6 inhibitor in combination with endocrine therapy in patients with hormone receptor positive advanced disease. Thank you.