Immunotherapy Continues to Move Into the Sarcoma Treatment Landscape

New agents and targets are being identified for treating sarcoma, making immunotherapy a bigger part of the conversation, says Breelyn Wilky, M.D.

You recently presented the phase 2 clinical trial looking at concurrent Inlyta and Keytruda in advanced alveolar soft part sarcoma, and other soft tissue sarcomas. Can you provide an overview of the study?

Wilky, an associate professor of medicine, Sylvester Comprehensive Cancer Care, University of Miami Health System, recently sat down CURE to discuss recent findings of a trial investigating Inlyta (axitanib) and Keytruda (pembrolizumab) in soft tissue sarcomas, as well as the role she envisions for immunotherapy in the treatment of sarcoma.This study is designed to sort of carry immunotherapy one step further. Immunotherapy has had some dramatic responses in sarcoma, but it doesn’t work for everyone.

One of the reasons people think immunotherapy may not be effective is that potentially there are problems getting the immune cells into the tumor. You have to have the immune cells in the right location for them to get turned on by the checkpoint inhibitors.

A lot of people, including Dmitry Gabrilovich, M.D., Ph.D., have done a beautiful body of research showing that a protein called vascular endothelial growth factor (VEGF) — which most people think of as being responsible for forming new blood vessels to feed tumors – also has direct effects on shutting down the immune system in tumors.

What were the most significant findings from this trial?

The concept of the trial is basically to use a VEGF blocker to sort of prime the tumor environment and hopefully get immune cells into the tumor, and then use the checkpoint inhibitor to turn them on.The trial is currently in progress, so we don’t have any official findings as of yet. We have currently put on 13 of the 30 planned patients. There are several patients with alveolar soft part sarcoma, but also other histologies in soft tissue sarcoma.

At this point, what I can say is that we have not seen any prohibitive, severe toxicities from the regimen, people have been able to do the regimen. As far as the results, we still have patients being treated on the study, so I can’t comment on any findings as of yet.

Our hope is that we will finish accruing the study probably within the next six months, so my goal is to have at least some preliminary data for next year’s American Society of Clinical Oncology (ASCO) Annual Meeting.

There were recently updated results presented from the SERCA2a study looking at Keytruda. Can you discuss those findings?

I think we’re all really excited to see the correlative studies, which will hopefully offer some clues as to how to pick the patients this treatment is most likely to help -- that we didn’t see. However, what was nice to see is the data showing that these responses, when they do occur, tend to last a longer period of time. To me, the results from SERCA2a just continue to tell us there is a signal for a select group of patients, and it just makes me more inspired to try and figure out who those patients are and how to make it work better for more patients.

Can you talk a little bit about what role you think immunotherapy will play, or what role you would like it to play in the treatment landscape of this disease?

Absolutely. Dr. Tap yesterday said it beautifully when he showed the five pillars of cancer care, and I think many people are convinced that immunotherapy is here to stay. I do believe that we’re just beginning to look at this in sarcoma and to understand how to use it properly.

I think the perfect scenario in the future would be when a new sarcoma patient comes to you, you have the ability to do a biopsy and profile that tumor, including for how active the immune system is in these various features within the tumor. That way, you can make your selections from your different treatment modalities, whether it’s chemotherapy, whether it’s immunotherapy, or targeted therapy, and really customize treatment for sarcoma much more detailed than we currently can.

Can you talk about the strategies involved with deciding which agents suit which patients best?

When I think about how I’m going to treat a patient with sarcoma, the pathology and the biopsy is really key. You want to know exactly what type of sarcoma this is because there are over 100 different types, and then you look at the patient. Know the tumor and know the patient.

There are some patients that may be great chemotherapy patients — they’re super young and super healthy. And then there are others that might not be able to tolerate that significant of treatment, so we customize all along the way. But certainly this particular histology, and I think hopefully in the future more genetic information and hopefully more immuno-profiling information will help us customize even further.

What would you like to see in this treatment landscape in the next five to 10 years?

Immunotherapy, immunotherapy, immunotherapy. I am so incredibly excited because there are tons and tons of new drugs and new targets within the immune landscape that other cancer types are furiously going through research to identify and learn how to use.

What I would like to see is that in five to 10 years, let’s say we decide that a patient is a good candidate for immunotherapy. I don’t just reach for a checkpoint inhibitor, I reach for a sort of cocktail therapy, kind of like what we do for HIV infection nowadays where you don’t just hit it with one method, you hit it with multiple methods all at the same time. So maybe for sarcoma that means the patient gets a vaccine, or the patient gets T-cell directed therapy first, followed by a checkpoint inhibitor and maybe treatment to also inhibit either T-regulatory cells or suppressive macrophages, and ideally all of that information would be guided by what is actually currently existing in the patient’s own tumor.