Everolimus for non-functional neuroendocrine tumours

Prof James Yao - University of Texas MD Anderson Cancer Center, Houston, USA

We have done a series of studies with everolimus in neuroendocrine tumours beginning with small, single institutional studies and then leading to the larger, multinational, multi-centre RADIANT studies.

What was the rationale for using everolimus in this setting?

We observed that patients with genetic cancer syndromes in the mTOR pathway developed neuroendocrine tumours. That’s really what led us to develop a series of studies that showed that there’s activity for everolimus in neuroendocrine tumours.

Why look at non-functional tumours?

Back in 2011 we completed RADIANT-3 and showed everolimus was active in pancreatic neuroendocrine tumours and got the drug approved for that group of diseases in 2011. There’s a big gap in terms of treatment for non-functional tumours. These tumours tend to be a little bit more aggressive, they grow a little bit faster, diagnose a little bit later, survival is shorter. That’s the motivation for us to see where else everolimus can really contribute.

Would you say this was an unmet need?

The best analogue where it has really shown to be active is in patients who are treatment naïve or mostly stable. There is a large group of lung neuroendocrine tumours where there’s really no drug really showing activity in terms of being able to stop tumour growth. So there is still a lot of unmet need which this study fulfils.

What were the results of your research?

This study in which we compared everolimus to best supportive care and placebo, we showed an improvement in progression free survival from 3.9 months to 11 months by central radiology review. This is essentially a 52% reduction in the risk of disease progression and that’s really the primary endpoint of the study. We also showed there’s a trend towards improving overall survival at this very early, first interim analysis and we’ll be continuing to follow the overall survival once the data matures.

Do you think this is practice changing?

I think it definitely offers a new treatment option for patients where there are truly no treatments available, especially in the lung group and in patients’ non-functional tumours that are progressing.

What should doctors do to address neuroendocrine tumours, especially those that are non-functional?

I think we’re beginning to see an era where we have more treatment options available. Everolimus, and our plan is to essentially present these results in the peer-reviewed literature as well as seeking health authority approvals.

What’s the take-home message for clinicians?

This year we have a very big year in neuroendocrine tumours. We have a number of phase III studies showing significant activity and everolimus here really has now demonstrated broad activity across a wide range of neuroendocrine tumours – in lung, in pancreas as well as in the gastrointestinal tract. That’s really the first of its kind in terms of treatment in neuroendocrine tumour that demonstrates such a wide ranging activity across the different sites.