ASCO 2015

Novel targeted drug palbociclib slows progression of hormone receptor-positive breast cancer

Dr Nicholas Turner - The Institute of Cancer Research, London, UK

You’ve been looking at a very interesting drug, palbociclib, what is it and what was it doing and why were you looking at hormone receptor positive, HER2 negative patients?

Palbociclib is an inhibitor of cyclin-dependent kinase 4 and 6, CDK4 and 6. These are genes that are known to be key to the growth of hormone receptor positive breast cancer and palbociclib is a drug that inhibits these and stops breast cancer from growing.

So what did you do in the study?

In the study we took women with hormone receptor positive, HER2 negative advanced breast cancer who had progressed on their prior endocrine therapy. They were then randomised to either palbociclib in combination with an endocrine therapy, fulvestrant, or fulvestrant alone.

What was it that palbociclib was expected to do for them?

It was expected that palbociclib would be beneficial for these women but the study stopped early at the interim analysis because the degree of benefit that was seen with palbociclib was really quite high.

In fact I saw your curves, they were well separated, weren’t they?

Yes, they are well separated. There was an over doubling in disease control, progression free survival, with palbociclib and fulvestrant.

Although therapies are so good in this context that you didn’t get a difference in overall survival?

Well at this point the study stopped early at the interim analysis because of the degree of improvement in progression free survival. So there have been few deaths on the study. The study blind has been maintained and we continue to follow-up and we will report the effects on overall survival at a later date.

And the hazard ratio is less than a half so it’s benefitting… it’s a big benefit.

Yes, I think that it’s a big benefit but importantly also palbociclib was well tolerated for these women.

So what kind of side effects did you get?

We saw very frequent blood test abnormalities, the most common being low white blood counts but it was very rare to see a complication of this. So the most common side effects were tiredness and a mild rate of hair thinning and mouth soreness.

So what do you think are the lessons, the clinical lessons, coming out of this quite impressive looking study?

I think that it’s important for this group of women because one of the alternative treatment options is chemotherapy for them. So this shows that this active combination can really substantially defer the point where a woman would need to consider chemotherapy.

Is there a downside to using this new agent?

You know, it does have some side effects and it will of course have a cost associated with it. But it appears to be quite active in the clinic.

What about patient selection too?

This study looked at a large group of breast cancers, hormone receptor, HER2 negative breast cancer which had progressed on their prior endocrine therapy. This is the most common subtype of breast cancer.

So what message would you like doctors to take home from this announcement you’ve made here at ASCO?

The message, I think, is that palbociclib is an active drug that is well tolerated and we will look forward to when it will be available in the clinic.