Genomic-driven clinical studies in breast cancer

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Published: 4 Jul 2017
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Prof José Baselga - Memorial Sloan Kettering Cancer Center, New York, USA

Prof Baselga speaks with ecancer at WIN 2017 about widening trial targets and patient participation for new therapies against breast cancer.

He introduces phase I studies of taselisib, now escalating to a phase III study (SANDPIPER) combining the PI3K inhibitor with fulvestrant, aiming to improve specificity and toxicity compared to previous studies.

Prof Baselga discusses Akt inhibitors as single agents and used alongside immunotherapies, and a network to streamline patient recruitment to relevant clinical trials.

I presented our efforts in breast cancer and beyond on precision medicine. I began presenting our sequencing effort – what do we do with our platforms. The highlight would be that we are sequencing 700 cases a month and we have a huge pile of genes and basically those genes we then integrate them into our database and we try to identify patients for a number of clinical trials. So I presented data on about twenty basket trials and focussed on those that are perhaps most active in breast cancer. So I’m talking about targeting PI3 kinase, AKT, ERBB2 and others. Taselisib is a good example, it’s a very potent PI3 kinase alpha inhibitor. I presented data that we just published in Cancer Discovery, the phase I study, showing a very nice response rate and then these rationales for combining taselisib with fulvestrant. That is the basis for the SANDPIPER study that is the phase III randomised registration study that we just almost finished enrolment.

Would that be advancing on the BELLE-2 trial?

BELLE-2 was in a similar patient population, the difference is that the drug that we used there was a pan-PI3 kinase inhibitor. So although we saw increased activity, no question, the side effects were quite profound. The importance of taselisib is that it’s actually more active but has less toxicity than the drug that was studied in BELLE-2.

A proportion of breast tumours express AKT mutations such as the E17K. So there is a rationale to target AKT in those tumours, that’s one approach. The other approach is that we have conducted clinical trials in triple negative breast cancer in which we have combined AKT inhibitors with chemotherapy and we have found quite interesting response rates. So we’re going to be launching also a phase III study in that population.

What does this data mean for clinical applications?

It’s very complex, as you can imagine. The complexity of this data is huge so we need to provide them with tools to be able to navigate through the data. What we have is a computer-based system in which whenever we identify, based on the genes, that a patient may be eligible for a clinical trial we send an email to the physician and say, ‘Listen, you’re going to see this Mr Smith on Wednesday. Mr Smith may qualify for this trial, can we help you in providing information for the patient? Can we help you in considering this patient into the clinical trial?’ So we have what I like to call a rapid clinical trial intervention force that we assist the physician. It’s a huge issue and 480 genes, you are in clinic, it’s impossible. The job of our physicians has to be supported because they cannot do it.

Could patient advocates be a useful bridge between patients and clinical trials?

This is front and centre, we are working very closely with incredibly engaged patient advocates. As a matter of fact, we have created at our institution what we call a patient family and friends advisory committee and they are present not only in our IRPs but also more importantly they are present in the way we roll out clinical trials. They give us a lot of feedback, for example one thing that is fascinating is that we are changing the way that we provide informed consent. You can no longer read these consents, they don’t make any sense. Physicians don’t know what they are doing. So with the help of patient advocates we are developing new tools so now our informed consents are videos and we have videos that the initial ones are not of great quality but we’re improving the quality and the idea is to make things understandable. We would like actually, as a matter of fact, to have the patients look at the videos before they come to clinic so they can then try to see what they understand, what they don’t understand and then have a much more meaningful interaction in the clinic. Imagine the situation, the patient comes to clinic, they don’t know what’s going on and you explain to them. Within ten minutes it’s not possible that they have an understanding nor they can even feel a question. So when they leave the clinic then they have a zillion questions that they have to make another appointment. So we need to change our care delivery process.

How can people get involved?

There are many opportunities through co-operative groups and many opportunities through trials that are opening in multiple sites. The NCI-MATCH is an example. At Memorial Sloan Kettering we have our own networker sites. We are here, just get in touch with us.