Impact of precision medicine in refractory malignancies

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Published: 6 Jun 2016
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Prof Maria Schwaederle - University of California, San Diego, USA

Prof Schwaederle speaks with ecancertv at ASCO 2016 about her meta-analysis of personalised therapy (selection based on biomarkers) in phase I studies.

Pooling data from 346 trials of personalised therapy versus those without, comprised of a total of 13,203 patients, her team found that personalised therapy correlated with improved response rate (RR) (30.6% vs 4.9%) as well as prolonged median progression free survival (PFS) (5.7 vs 2.95 months).

Analysis of trials arms utilising biomarker targeting (N = 234 arms) showed that a biomarker-based strategy statistically improved RR compared to targeted arms that lacked a biomarker-based approach (31.1% vs 5.1%), and further that a “genomic (DNA) biomarker” had higher RR than those using a “protein biomarker” (42% vs 22.4%).

Prof Schwaederle highlights the success of personalised therapy trials as potential for phase I trials to move beyond being a proof-of-concept, and recognised as therapeutically important for patients.


ASCO 2016

Impact of precision medicine in refractory malignancies

Prof Maria Schwaederle - University of California, San Diego, USA

This year at ASCO I’m going to present a meta-analysis of over 13,000 patients and our results, our findings, that are showing that with the use of a biomarker which is the basis of personalised medicine we can really improve patients’ outcome. So we ran this analysis with a lot of  different experts in the field across the nation, including Dr Razelle Kurzrock who is leading the Department of Precision Medicine at UCSD San Diego Moores Cancer Center.  So we decided to study this because even if it’s pretty intuitive that the use of a biomarker would improve patients’ outcome, there is still quite a bit of debate as to what is the actual impact of the use of a biomarker. We think that this debate is particularly important in the phase I setting where there is a very traditional belief that phase I studies are not about efficacy but they are mostly about assessing side effects and toxicity of new drugs. So that’s the main reason why we decided to study this.

Our main findings, and we think that the results are quite striking, is that the use of a personalised approach, so when we select patients with biomarkers, led to response rates of about 31% versus only 5% when we didn’t use a biomarker. We also had similar results with PFS, which is the progression free survival. So when we select patients with the right biomarker we had a progression free survival of 5.7 months versus a little bit less than 3 months without a biomarker based approach. So this is really the main finding of our study.

But there a couple of other things that really deserve to be mentioned here too. The first thing is that targeted therapies in and of themselves were not effective, they really need to be paired with a biomarker. Indeed, if we use targeted therapy without selecting the right patients, we found in our meta-analysis that the response rates were quite low, about 5%, which is in fact comparable to the results that we have with regular chemotherapy. So that’s the main second finding conclusion we have in our study.

The last thing that is quite important too is that when we compared within personalised trials the type of biomarker, so we compared if the biomarker was genomic versus protein, and we found that genomic biomarkers performed better. Indeed, the response rates with genomic biomarkers were above 42% which is pretty impressive in the phase I setting, it’s even pretty high for an FDA approved drug.

So overall we found that a personalised strategy which is the use of a biomarker based approach led to improved outcomes for patients even in a phase I refractory population. So they studied new drugs in a relatively small population of patients and these patients have exhausted, for most of them, multiple lines of prior therapy. So these are very difficult to treat patients. Even in this refractory population we can get a really high response rate, 42%, with the use of genomic biomarkers. So we really hope that our findings can help reshape the intent behind phase I clinical trials and that more patients can enter clinical trials with the intent of having a real efficacy and not only to test the toxicity of new drugs.

It sounds like huge benefits.

Yes, yes. We really think it could change a lot and that phase I trials could be used as therapeutic instead of only being used to test the safety and the side effects of drugs.

Are there any plans to advance this investigation into other trials or with treatment naïve patients?

Yes, that would be something very interesting to do also. It’s not mostly done now so most of the time patients for whom we do personalised therapy have exhausted multiple lines of therapy but we really think that there might be a higher benefit if we could treat patients a lot earlier. So it’s like if we give the example of imatinib for CML, these patients when they are treated earlier diagnostic with the right drug, which is imatinib which is targeting BCR-ABL patients, we really have improved survival. In the past it was about four years of survival and now with this new drug when it’s given very early in the disease course the survival is about 25% and we really think that we could transfer this model to solid tumours too.