The emerging role of immunotherapy for the treatment of early and advanced breast cancer

Dr Rita Nanda - UChicago Medicine, Chicago, USA

The educational session yesterday that I participated in was focussing on updates of what’s going on in the immunotherapy world for triple negative breast cancer. It also focussed on toxicities that we’re seeing and how to manage those toxicities. Then it ended with a talk by Dr Rem [?] who focussed on PD-L1 testing and the complexities of that in real world practice.

What were the session highlights?

Most of what I spoke about were updates in the last year of immunotherapy agents for breast cancer. It was a really exciting year, I think immunotherapy has certainly arrived for breast cancer. We got our first approval for the combination of atezolizumab and nab-paclitaxel for metastatic triple negative breast cancer that expresses PD-L1 in March of this year. So that was really exciting. Then also we’re seeing emerging data on new combination strategies including PD-L1 inhibition with chemotherapy and MEK inhibition and AKT inhibition which all looks very promising in the early stages, in the phase I, phase II settings, for metastatic triple negative breast cancer.

Then what we also saw at ESMO this year was the KEYNOTE-522 data which shows an emerging role for pembrolizumab plus standard neoadjuvant chemotherapy in the early stage setting for triple negative breast cancer where we saw a significant and dramatic improvement in PCR rates for women with early stage triple negative breast cancer as well as an improvement, or at least a trend to improvement, in event free survival which is really exciting to see. So I think we’ll all stay tuned because that very well could be a practice-changing trial.

Have there been any improvements in related toxicities?

The toxicities that we’re seeing with immunotherapy are pretty standard across disease types. The one toxicity that we have seen with a higher incidence than what’s been seen in other tumour types in other trials and in other disease settings is adrenal insufficiency. So in early stage clinical trials, both the I-SPY 2 trial, which I led that looked at pembrolizumab in conjunction with neoadjuvant chemotherapy that was taxane and anthracycline based, as well as the KEYNOTE-522 trial which incorporated carboplatin into the mix, we did see significantly higher rates of adrenal insufficiency that have been seen in other diseases, in other tumour types and in other disease settings. So that is the one toxicity that has been shown before to be present but with a higher incidence in early stage breast cancer. The reasons for that are unclear so we certainly need to explore that and understand why that is. But in the meantime we need to focus on being very vigilant about identifying those patients who may have toxicities that are immune related and managing them very aggressively early on.

Is PD-L1 testing now routine in clinic?

It is. The FDA approval for atezolizumab and nab-paclitaxel in advanced triple negative breast cancer is specifically for PD-L1 positive disease. So there are a lot of different tests out there, a lot of different ways to score PD-L1 positivity and Dr Rem [?] really highlighted that in his talk and the potential for difficulties with reproducibility of what’s positive and what’s negative. But I am doing it at this time. I’m using the SP142 VENTANA assay which is the companion diagnostic for the approval but I know that certainly out there in the community people are using what they’ve got available.

What does the future look like for immunotherapy?

This is just the tip of the iceberg for breast cancer. We already have an indication for advanced stage disease. I suspect an indication for early stage disease will be coming in the not too distant future and hopefully we’re going to be curing more and more women with early stage triple negative breast cancer. So we’ll be seeing a dramatic reduction in those women who ultimately will recur.

Is there anything you’d like to add?

There are going to be some interesting highlights in this meeting. We’re going to get an update of the KEYNOTE-522 data later in this meeting from Dr Peter Schmid. We’re also going to be getting the NeoTRIP neoadjuvant data that will be presented in the open session on Thursday. So it will be exciting to see the data as they emerge and how we are able to incorporate these therapies into the treatment for both women with advanced stage disease and hopefully in the not too distant future for women with early stage disease.