ASCO 2015

Letrozole vs observation for HR positive breast cancer

Dr Nicholas Zdenkowski - University of Newcastle, Newcastle, Australia

We were trying to find out whether an additional five years of letrozole would reduce the rate of invasive breast cancer events in women who previously received at least four years of any adjuvant endocrine therapy and had a one year break.

Can you put this into the context of what has been happening? Because there has been quite a bit of talk. One of the people, Richard Peto, said longer is better quite a few years ago now. What was the context of this?

This trial opened in 2007 and prior to that we had evidence that five years of an aromatase inhibitor was effective, five years of tamoxifen was effective and five years of tamoxifen followed by five years of an aromatase inhibitor was effective. We did not have evidence about whether it was effective to continue after any adjuvant endocrine therapy including aromatase inhibitor and we didn’t have evidence about whether it was effective to have a gap after the five years of endocrine therapy. So there were two issues there, there was the issue of whether it’s effective to have the gap because these patients are at risk of a new breast cancer as well as a recurrence of their previous breast cancer. So there were two aims – does it prevent a recurrence of the previous breast cancer, does it prevent a new breast cancer occurring?

So could you tell me how you constructed the study, what did you have to do?

Originally it started out as a phase III trial with the superiority endpoint of being invasive breast cancer events and we were planning on 1,700 patients. It was a placebo controlled study but due to slow recruitment unfortunately we were unable to complete accrual and we stopped after 360 patients.

So what did you find, in fact?

The study primary outcome of invasive breast cancer events was significantly reduced in the letrozole arm. So there were 15 invasive breast cancers identified over three years in the observation arm and 2 in the letrozole arm.

Wow, that’s a big difference, even though you didn’t recruit the number of patients you wanted.

Yes, exactly. It was better than we could have hoped.

What did you conclude from this rather interesting finding?

It’s something that confirms what a lot of people have thought about that longer endocrine therapy is better and that a lot of patients will benefit from that prolonged endocrine therapy. Now we need to know which patients they really are because we need to select these patients better.

Did you throw any light on the gap versus no gap?

There was a median gap of 2.7 years between completing previous endocrine therapy and starting this study. So I feel that these patients could potentially stop their endocrine therapy after five years and have a bit of a gap if they’re not tolerating that well and then restart if they’re keen. That helps in clinical practice.

I know you’ve got some reservations about individualising therapy but what do you think clinicians could make of your findings with letrozole?

I think that it’s a safe treatment and for patients who are in the higher risk categories I think it would be very reasonable to continue on with an additional five years of endocrine therapy after any prior endocrine therapy.

What do you think this might tell us about other endocrine therapies being prolonged beyond the five years?

We’re waiting on a couple of studies of prolonged endocrine therapy and they will be confirmatory trials.

What do you think is the overall take home message from this for cancer doctors, briefly?

That prolonging endocrine therapy is a safe and potentially effective treatment, from this study, to reduce the rate of breast cancer events.

And in terms of the number of patients needed to treat, that must be quite significant, quite a few patients.

The numbers needed to treat to prevent one invasive breast cancer event is 14, which is quite favourable.