What was your presentation today?

I’ve attended some and I will be doing a presentation in around an hour and a half highlighting sarcoma regarding the recent data and the presentations done during ASCO 2023.

Could you elaborate on the studies presented?

Sarcoma, I have been seeing patients with sarcoma now for more than a decade and it can be very frustrating because it’s a very heterogeneous disease. The last time I checked, probably we have more than 50 diseases, we call them all sarcomas. Most of these studies we include all of them, or at least half of them, and that’s why we don’t really get great results until recently.

Now, sarcoma for decades, believe it or not, the only drug that was approved by the FDA was doxorubicin in the ‘80s and ‘90s and 2000s. But in 2012 that started to change and we got pazopanib approved in soft tissue sarcomas. Then we got targeted treatment, we have pexidartinib approved in two rare sarcomas such as the pigmented villonodular synovitis as well as tenosynovial giant cell tumour. Then we had other targeted treatments approved recently atezolizumab in alveolar soft part sarcoma. 

We really think the FDA is going to approve a very unique drug in desmoid tumours. Desmoid tumours are benign but they cause a lot of trouble because they invade locally and cause a lot of morbidity. Although they don’t metastasise, they cause a lot of morbidity in these patients. There is a drug called nirogacestat which is a gamma secretin inhibitor that hopefully will be approved based on the DeFi study - phase III randomised between the new drug, the gamma secretin inhibitor, or placebo. That was published recently in The New England showing that the hazard ratio for the progression free survival is 0.29 – highly, highly significant. It’s an oral agent, it’s very effective but it has side effects. One of the prominent side effects of this drug I don’t think anyone really anticipated was the ovarian dysfunction. Many of these desmoid tumour patients, because it’s oestrogen dependent, occur in young women. We really need to pay attention to that.

In terms of recent, recent data presented during ASCO, it’s all about immunotherapy and chemotherapy and tyrosine kinase inhibitors. Sarcoma is one of those rare diseases that actually immunotherapy doesn’t work. But when combined with chemotherapy it has been shown in many abstracts and presentations to be very effective when used in the right group of patients.

Could you provide an overview of the comprehensive cancer care services available at Memorial Cancer Institute?

We work with a lot of people on the clinical trials and something we offer now is a combination of immunotherapy and chemotherapy. Immunotherapy alone, like I said, has not worked, actually, it can be really dangerous. The reason is that over 50% of patients when we give them immunotherapy, even as a doublet, not just a PD-1 inhibitor but a CTLA-4 inhibitor, they get actually progressive disease. It’s not that they don’t respond, they actually progress.

So combining immunotherapy with chemotherapy is really a very promising venture for these patients but also how to use that. Actually I will be presenting some of the abstracts. There were two abstracts using what we call priming. Priming is using chemo alone first or immunotherapy alone. There was a study from the German group where they used trabectedin, an FDA approved drug in sarcoma, for four cycles and then introduced the immunotherapy in cycle 4 because chemotherapy acted as debulking. Then you get the immunotherapy to work not just with chemotherapy but also as maintenance.

Another presentation from the group in Colorado, they actually primed patients with immunotherapy first and then they added chemo. I don't really understand that rationale because I just told you that patients on immunotherapy, more than 50% of them progress on the treatment.

A really interesting concept in sarcoma where, although I told you that immunotherapy doesn’t work, we’re not giving up on it. I think it works, we just don’t know how to use it. 

There was actually an abstract with an agent called TTI621. This is really a very unique agent, it’s a monoclonal antibody. In our bodies there are some cells that are created but we need to protect them against the phagocytes and macrophages so that they don’t eat them, literally. Those cells acquire an antigen called CD47, cluster designation 47. Sarcoma cells have this protein and what happens is this protein binds to another protein on the phagocyte telling the phagocyte ‘Please don’t eat me.’  So we need to pluck that, it’s what we call a macrophage checkpoint system. The TTI621 is a monoclonal antibody against CD47. What happens is the antibody binds to CD47 thereby preventing it from binding on the phagocyte to tell the phagocyte not to eat it. That’s a really promising technique. There is data about the low dose cohort in that study. There were some responses but the immunotherapy there was working with chemotherapy including doxorubicin. Very few patients; we are waiting for the high dose cohort that is ongoing but that’s really promising.

Again, immunotherapy will be used in sarcoma, we just need to get smarter how to use it.