Good morning everyone. So we go from the most aggressive, less frequent, type of breast cancer to the most frequent and least aggressive, in general, type of breast cancer. So we presented an overall survival analysis of the PALOMA-3 study. The PALOMA-3 study is a study that was designed back in 2010 with a new drug testing palbociclib, one of the first in class CDK4/6 inhibitors. The intention at that time, considering the exciting data coming from an early phase II, was to find out if this drug in combination with fulvestrant was going to improve the progression free survival in patients that had progressed on endocrine therapy. This is the most common situation, so we have 65% of patients of hormone receptor positive breast cancer so the majority of metastatic breast cancer patients are ER positive. All these patients progressed on endocrine therapy. We showed at the first interim analysis, there was actually the data in December 2014 and published for the first time in July of 2015, that there was an improvement in progression free survival, statistically significant, from 4.6 to 9.5 months.
This follow-up continued, we had a number of correlative studies, another endpoint. The drug is very well tolerated, the quality of life is improved, the patients have a prolongation of time for chemotherapy.
So today is the first time, with a median follow up of 44.8 months, we are able to look at overall survival, keeping in mind it has been extremely difficult for this group of patients to show an overall survival advantage. So these are my disclosures.
This is the overall survival in the intent to treat analysis comparing the two groups: the palbociclib plus fulvestrant median overall survival 35.9 months compared to a median of 28 months. What is important with regard to this data, as I told you, these patients have many treatment options, receive a median of three lines of therapy in the placebo group, up to ten lines of therapy after they progress, that the absolute improvement that we have seen in the progression free survival is actually maintained in the group treated in the overall survival analysis, 6.9 months. It’s important also to consider that the study was designed to stratify patients based on visceral metastases, sensitivity to prior endocrine therapy. So patients had progressed later during the adjuvant therapy or they had already got some benefit from first line endocrine therapy. Every patient was already exposed to at least two lines of therapy or more. So when we look at the stratification patterns patients have been exposed and they have been already showing endocrine sensitivity versus endocrine insensitive, keeping in mind the vast majority, more than 400 patients of 521 patients, had in fact endocrine sensitivity. We see that the magnitude of benefit is even larger. There is an improvement of 10 months in overall survival in the palbociclib arm versus placebo arm and this is quite significant even though that was a secondary endpoint. 39.7 months versus 29.7 months.
We also show in the data that there is a fraction of patients, 15%, that even though the study did not allow a crossover eventually down the road later, for physician’s choice received a CDK4/6 inhibitor. That could have impacted even more the difference in overall survival, so somewhat decreasing the difference. So there is a statistical adjustment that can be done and shows that the magnitude is even larger, much larger than we see here with the sensitivity to prior endocrine therapy. The other group is a very small group.
So we wanted just to make the point that the progression free survival at the last follow-up, this is data from October 2017, 6.6 months is still maintained and the same magnitude of benefit is shown in the overall survival – 25.9 months and 28 months.
So our conclusion is that in patients with hormone receptor positive, HER2 negative advanced breast cancer the combination of palbociclib and fulvestrant shows a clinically meaningful improvement in overall survival and this is explained much more in detail in the paper in the presentation today. There is an absolute difference of 6.9 months, similar to the progression free survival difference of 6.6 months. There is a significant 10 months improvement in overall survival in patients who have prior sensitivity to endocrine therapy.
Importantly, this drug did not interfere with the efficacy of other standard treatments after progression. Patients went on to receive chemotherapy and other, different, lines of therapy. The safety profile did not change, even with the longer follow-up and we concluded these findings confirmed that the use of palbociclib plus fulvestrant is a standard of care now in patients with previously treated hormone receptor positive, HER2 negative advanced breast cancer.