Analysis of assay used in IMpassion130 to guide treatment of metastatic and advanced breast cancers

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Published: 31 Oct 2019
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Prof Sherene Loi - Peter MacCallum Cancer Centre, Melbourne, Australia

Prof Sherene Loi speaks to ecancer at ESMO 2019 in Barcelona commenting on the post-hoc analysis of the IMpassion130 trial.  

The IMpassion130 trial found that PD-L1 positive patients with advanced or metastatic breast cancer benefitted from the addition of atezolizumab to their treatment.

However, Prof Loi explains that the issue with PD-L1 testing is that there are lots of assays that could be used to determine whether a patient is PD-L1 positive. The post-hoc analysis aimed to understand how different assays compared to the currently approved SP142.

Prof Loi discusses how SP142 compared with SP263 and SP223C and how these insights may impact clinical practice.

IMpassion130 was approved on an assay called SP142. That’s an assay which was used in the trial and it classified 40% of the population as PD-L1 positive on their immune cells. So that was the population that derived the benefit from the addition of atezolizumab. The issue with PD-L1 testing is there are lots of assays and lots of ways to call positivity. What we wanted to understand in the abstract presented by Hope Rugo was how these different assays compared. So we looked at SP263 and the 223C assay which is the Merck assay. I won’t bore you in the specifics but basically we found that SP142 classified the least number of patients as positive, 263 and the 223C assay classified about 60% more patients as positive. When you look at the benefit of atezolizumab the hazard ratios do look roughly the same across all assays which suggests to me that potentially more people can benefit. But if you look specifically at the patients that were negative by the 142, which is the approved assay, and positive by the other assays it does seem that their hazard ratios are a little bit larger. So maybe they don’t benefit as much.

The 142 assay is reading out a truly sensitive population. It’s difficult to understand how we’re going to implement that in the clinic because obviously pathologists find they have to buy different equipment. Specifically for breast it may be harder to get reproducibility so a positive over here in this lab may not be the same as another lab and that’s, of course, important for patients. It means less patients potentially would get the drug. But we need to understand a bit more whether we can find other markers that will help us understand who will benefit. So overall it was a nice study to look at the different assays but at the end of the study we feel that the assay used in IMpassion does pick out a sensitive population that will benefit from the addition of atezolizumab.