Utilizing Immunotherapy To Treat Patients With Early Breast Cancer

CONOR KILLMURRAY
Tuesday, October 22, 2019
Immunotherapy is not often associated with treatment in the early stages of breast cancer, but new findings from the Keynote-522 study showed that this could be a viable option for patients with early breast cancer. This was the topic of discussion amongst experts that traveled to Barcelona, Spain, for the European Society of Medical Oncology (ESMO) 2019 Congress. 

At ESMO OncLive®, a sister publication to Oncology Nursing News®, had the chance to speak with Rebecca Dent, MD, medical oncologist at the National Cancer Centre in Singapore, on the findings of keynote-522, as well as, where she sees the future of immunotherapy in treating early breast cancer. 
 
OncLive®: Why should immunotherapy be incorporated in treating patients with early breast cancer?

Dent: I think certainly what we've learned is that in early breast cancer, the immune microenvironment is different than a metastatic breast cancer. Looking at simply like something like TIL, you can see there's a much lower rate of TILs. So, the immune system is dampened as patients progress through advanced disease. The early setting, ironically, is ideally suited to try and interrogate with immune checkpoint inhibition. Now we've seen this clinically where in the first line second setting, second line setting, third line setting, immune checkpoint inhibition works earlier. In later line therapy, you only see responses in 5 to 6% of patients in the first line setting you see them in about a quarter of patients. So again, it makes sense that earlier on you're more likely to see a benefit.

So again, it makes sense that earlier on you're more likely to see a benefit. Now the bigger question is what should be the chemotherapy backbone? We know that certain chemotherapies actually can act like chemo modulators, immune modulators. So, if you look at specifically Platinum based chemotherapy, what we know is that action actually can suppress some of the immunosuppressive elements of breast cancer.

Can you discuss the results of the Keynote-522 study?

The keynote-522 study was looking at early triple negative breast cancer in the neoadjuvant setting. Really representative population with almost half the patients being node positive included PD-L1 positive and PD-L1 negative, but about 80% of those patients were PD-L1 positive. The backbone of this particular study was looking at it anthracycline taxing platinum, which is the most robust control arm you can have with the highest pathological complete response rates reported in the literature and this was plus or minus pembrolizumab in the early breast cancer setting, then the patients proceeded with surgery, and then they continued on either pembrolizumab or placebo. This was the first readout of the results that were presented at this meeting, which showed impressive improvement in pathological complete response rate, regardless of the definition used.

What other methods of treatment could be considered with chemotherapy?

For the longest time, we think of chemotherapy has just been chemotherapy, as a cytotoxic and I think different chemotherapies likely have some immunomodulatory effects. So, there was the TONIC trial also that showed us that chemotherapy can act as a primer. In addition, radiation actually, potentially can help us create new antigens that can present to the immune system. So, we’ve seen some really interesting data from our colleagues in lung and melanoma looking at combining radiation and checkpoint inhibition.

Now there are numerous other combinations that are being developed and I think that's where we have to really look down and sort of say, look at the immune profiling that we can now do, and you can see that there are certain ones that are inflamed, but they're also that, say, certain groups of patients that actually have an immune cold tumor that you need to figure out how do we activate those T cells? And so, these different combinations, I think, in the future are going to be what's most exciting. Can we convert a PD-L1 negative to a PD-L1 positive tumor? There are also many different combinations that are being explored, right now mostly in the metastatic setting, but I think that's the way of the future.
 

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