Immunotherapy Agents Emerging as Key Players in Sarcoma

Shannon Connelly
Published Online: Thursday, Dec 15, 2016

Breelyn Wilky, MD

Breelyn Wilky, MD

Excitement continues to surround the potential role of immunotherapy agents in the treatment of patients with sarcoma, according to Breelyn Wilky, MD.

In November, The European Commission granted an accelerated approval to olaratumab (Lartruvo) in combination with doxorubicin as a frontline therapy for patients with advanced soft tissue sarcoma, based on findings from the phase II JGDG study, which showed an 11.8-month improvement in overall survival (OS) with the PDGFRα antagonist versus doxorubicin alone.

In an interview with OncLive, Wilky, an associate professor of Medicine, Sylvester Comprehensive Cancer Care, University of Miami Health System, discusses recent findings of a trial investigating axitinib (Inlyta) and pembrolizumab (Keytruda) in soft tissue sarcomas, as well as the role she envisions for immunotherapy in this treatment paradigm.

OncLive: You recently presented the phase II clinical trial looking at concurrent axitinib and pembrolizumab in advanced alveolar soft part sarcoma, and other soft tissue sarcomas. Can you provide an overview of the study?

Wilky: 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, MD, PhD, 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.

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.

What were the most significant findings from that trial?

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 6 months, so my goal is to have at least some preliminary data for next year’s ASCO Annual Meeting.

There were recently updated results presented from the SERCA2a study looking at pembrolizumab. 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 future treatment landscape of this disease?

Absolutely. Dr. Tap said it beautifully when he showed the 5 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.


View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Medical Crossfire®: Optimizing Treatment and Management of Soft Tissue Sarcoma in Community OncologyNov 30, 20171.5
Moving Forward From the Status Quo for the Treatment of Soft Tissue Sarcoma: Key Questions & New Answers to Optimize OutcomesAug 16, 20181.5
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