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ESMO Breast 2021 | IO-IO combinations in metastatic TNBC

Marleen Kok, MD, PhD, Netherlands Cancer Institute, Amsterdam, Netherlands, talks on the use of immunotherapy (IO)-IO combinations for the treatment of metastatic triple-negative breast cancer (TNBC). Dr Kok comments on novel immune checkpoint inhibitors, including anti-LAG-3 drugs which are being explored in melanoma, and anti-CTLA4 drugs in breast cancer. Dr Kok also discusses cytokine-based treatments, such as NKTR-214, and oncolytic viruses. This interview took place at the virtual European Society for Medical Oncology (ESMO) Breast Cancer Congress 2021.

Transcript (edited for clarity)

It’s a pleasure to talk to you today about what we have been discussing at ESMO breast cancer and educational session on immunotherapy for metastatic triple-negative breast cancer or metastatic breast cancer, to say, because we also shortly discuss the options in ER+ and HER2+ breast cancer.

So, my specific talk, I have heard the fantastic talks of Professor Juliano and Professor Loi...

It’s a pleasure to talk to you today about what we have been discussing at ESMO breast cancer and educational session on immunotherapy for metastatic triple-negative breast cancer or metastatic breast cancer, to say, because we also shortly discuss the options in ER+ and HER2+ breast cancer.

So, my specific talk, I have heard the fantastic talks of Professor Juliano and Professor Loi. My talk was focused on combination immunotherapy, so immunotherapy plus another immune therapy, and these developments in mainly triple-negative breast cancer.

In summary, the field is still waiting for the novel breakthrough. Basically, the novel NTPD2, since now we are still working with anti-PD1. There’s no breakthrough regarding a novel immune therapy that will make a quick move to the first line, but I think there are interesting data on, together with anti-PD1, how we can change tumor microenvironment.

We discussed data, for example, on novel immune checkpoint blocking antibodies, mainly still targeting the T-cells. For example, anti-LEK3, of which you’ll see data at ASCO in melanoma, a positive Phase III trial. Looking forward to seeing how those data can be applied to breast cancer. We shortly discussed anti-CTLA4 that is a little bit disappointing in the field of breast cancer, not so many studies have been focusing on that target. I really think that that can induce durable responses, which are so important for patients with metastatic disease.

Other options we discussed were more the cytokine-based treatments. For example, the compounds called NKTR-214. It’s IL-2 based in which you can stimulate effector cells in a really broad manner, which have shown, I think, very interesting data, especially in the PDL1-negative population, for which we know that the anti-PDL1 blockade- you know, some patients respond better but the majority not. A stimulating index, a specific group of triple-negative breast cancer, might be very important. And we’ve also seen data on oncolytic viruses, on therapies that you can inject into breast tumor to mimic a virus. For example, a treatment based on a STING agonist, but everything is still in Phase I, early Phase II. Control arms are missing. It’s a bit hard to predict for what will be the future for our patients, but at least we see that many initiatives are around this IO combination.

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