Phase I taselisib results and a cell-free DNA assay

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Published: 25 Apr 2018
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Dr José Baselga - Memorial Sloan Kettering Cancer Center, New York, USA

Dr Baselga speaks with ecancer at AACR 2018 about results from a phase I basket study of taselisib to treat locally advanced or metastatic solid tumours harbouring a PIK3CA mutation.

He highlights how these mutations occur in a host of sites throughout the body.

Dr Baslega also describes results from the development of a cell-free DNA assay, allowing for early detection and monitoring treatment response.

Over the last few years we have been proposing that we could treat tumours across the different types with the same therapy for as long as these tumours have a gene driver that is common. So we have done some studies to prove the point with BRAF and with NTRK and other targets. The one that one of our investigators is presenting here, her name is Komal Jhaveri and I’m the senior author, is we are presenting the results of a basket trial for tumours that harbour PI3 kinase alpha alterations. What we have observed is that there is a variety of tumours, we’re talking about head and neck and others, that harbour this driver mutation in PI3 kinase or they have amplifications of the PI3 kinase gene and they are quite sensitive to these therapies. So we are quite excited since PI3 kinase alpha mutations and amplifications occur in multiple tumour types. So most studies are being focussed in breast cancer, and rightly so, but you’re going to have a whole set of tumours that harbour these alterations. We will show actually quite nice clinical activity and beautiful water plots showing that this is working.

So what does this mean for the future of the patient?

For the future of the patient what will need to do now is decide what we do next. I would like very much to have the possibility to explore registration studies in not just breast but in other tumour types as well. That’s the implication.

What was presented at AACR?

We are presenting here one of the alphas on beautiful work that is showing that we can detect, using good technology, next gen sequencing technology, that we go deep and that we can incorporate a number of assays, not just the classical NGAs but also methylation patterns and other copy number alterations, that we can really detect the presence of tumours by cell-free DNA. I think that the implication of that is that we could begin to visualise the possibility of using this technology to a) diagnose cancer earlier, so this technology could be a phenomenal tool to screen populations at risk and to have a shift in the diagnosis from advanced disease to earlier disease and therefore increasing the cure rates. Then also you could use this technology in these tumour types to monitor response to therapy. So the beauty of this is that you can repeat it, so you can look at it multiple times and that’s also quite exciting.

Does this make sampling easier?

Much more convenient to patients instead of having imaging studies that are not sensitive enough to pick it up. The most important thing is that this technology is going to be far more sensitive than imaging. But, on top of that, it’s clearly far more convenient to patients than just to have CT scans or MRIs. So we’re still going to be doing all these imaging tests but I’m assuming they’re going to be far less frequent than what we do now.

Then the third implication of all this is that these cell-free DNA assays are helping us identify also what therapies to choose because they are giving us genomic information about some of the key driver mutations that are present in the tumour. So it’s not only telling us the tumour is growing but actually at the same time it’s telling us this is the way you should target the tumour because you have these mutations that are indicative of a dependency.