This year I decided to write some longer posts from the ECCO/EMCC meeting owing to the amount of potentially paradigm changing data coming out. These in depth op eds will roll out over the next few days.
Quite a few people have been asking what my picks of the conference are, so here goes, in order of Wow factor (purely from my perspective):
- Everolimus BOLERO-2 data in ER/PR+ HER2- breast cancer
- Alpharadin in advanced prostate cancer
- T-DM1 in HER2+ breast cancer
- Vismodegib phase III data in basal cell carcinoma
You can read more about the Alpharadin data on the companion Biotech Strategy Blog, but I will put up a post in the pros and cons of this therapeutic later in the week. It’s going to be very interesting indeed to see how this pans out.
Why did I pick the everolimus (Afinitor) data first over the others?
Well, regular readers here on PSB will know that I’m a great believer in
a) targeted therapies and
b) identifying mechanisms of resistance to determine logical combinations
We know that the PI3K-mTOR pathway is dysregulated in hormonal sensitive breast cancer leading to resistance, so a logical approach would be to treat women whose initial AI therapy has failed with another, but add in an mTOR or PI3K inhibitor. That’s exactly the case here.
The results? Simply stunning!
Jose Baselga presented the BOLERO-2 data to a packed audience. When he showed the slide for PFS, there were gasps in the audience around me – a shift in favour of the treatment arm (everolimus plus exemestane) over control (placebo + exemestane) not of the usual 1-2 months, but 6.5 months:
The side effect profile was consistent with what we know about mTOR and Aromatase inhibitors. One thing I would very much like to see is some subset analysis to see what factors separated the super responders from the average responders. This trial tested the combination in a general unselected population, but it would be nice to see if any factors can be derived from the data that suggests what might be predictive of response.
While these results are a major paradigm shift in women with hormonally sensitive breast cancer, the big question is can we do even better?
We also know from basic science that mTOR upregulates AKT, so eventually adaptive resistance will occur through that route too, but you can see where the next round of logical therapies might emerge in future. The current batch of AKT inhibitor have some challenging side effects when used in combination, but next generation of inhibitors might have a more tolerable and improved side effect profile.
All in all, I thought the BOLERO-2 data were my pick of the conference for major practice changing data and I hope to see this data submitted for approval to the Health Authorities very soon. This development is very good news indeed for women with ER/PR+ breast cancer.