Expert Says Immunotherapy Not the "Magic Bullet" in Sarcoma

Katherine Thornton, MD

While there has been much discussion surrounding immunotherapy in sarcoma, it is too early for the community to get excited, said Katherine Thornton, MD, co-clinical director, Center for Sarcoma and Bone Oncology at Dana-Farber Cancer Institute.

“Immunotherapy isn’t quite the ‘magic bullet’ for sarcoma that it has been in melanoma, lung cancer, and other various diseases—but we are still learning a lot,” she added. “The jury is still out on whether we are going to have immunotherapy be the ‘holy grail’ for our tumors. Right now, I don’t see it happening.”

There has been some limited success of immunotherapy in sarcoma.

Pembrolizumab (Keytruda) was investigated in 7 different subtypes of previously treated sarcoma in the phase II SARC-028 trial.

In this study, the best response rate was seen among patients with undifferentiated pleomorphic sarcoma. Of the 9 evaluable patients in that subgroup, 4 had a partial response (PR) and 3 experienced stable disease (SD). Among patients with liposarcoma (n = 9), 2 had a PR and 4 had SD. In the synovial sarcoma cohort (n = 9), 1 patient had a PR and 2 had SD. In leiomyosarcoma (n = 10), no patients experienced a PR and 6 had stable disease.

OncLive: Where are we at right now with immunotherapy in sarcoma?

However, many questions still remain regarding this and other immunotherapy trials for sarcoma, said Thornton. In an interview with OncLive, the expert discusses the potential that immunotherapy agents could have, as well as the role of genomic profiling in understanding the patients who may benefit from select treatments.Thornton: There were 2 larger trials that were presented in June at the 2016 ASCO Annual Meeting. One was a specific anti—PD-1 therapy in uterine leiomyosarcoma, and the other one was an all-comer sarcoma trial looking at pembrolizumab.

Unfortunately, in my mind, they were both really resounding thuds on the floor. There were no responders in the uterine leiomyosarcoma trial and only a handful of responders in the all-comers trial. They did report out the negative study, which I was really appreciative of because it is important to hear about the negative studies as well as the positive studies.

They made a lot of ado about the few responders who were in the larger pembrolizumab study—trying to stir up some excitement. There are a lot of questions that remain. The biggest question for me is, “Why did those patients respond when the vast majority of patients did not?”

In what area is the immunotherapy research happening?

What role does genomic testing play in the treatment of sarcoma?

That is what we are trying to figure out right now. There are certainly a lot of trials that are still speculating, and I do have patients coming to my clinic requesting immunotherapy. However, off of a clinical trial, I am very hesitant to use them with patients.Synovial sarcoma is one of the sarcomas that has traditionally responded to immunotherapy-type treatments in the past, and there are a fair amount of trials right now looking at synovial sarcoma as well as looking at myxoid liposarcoma. Those are some areas that are a little bit more exciting in the immunotherapy realm, but a lot is still unknown. The correlative studies that go along with the clinical portion are really going to tell us more information as we go forward.There have been some opinions on whether it is helpful or not. It is something that can open up some opportunities. There is such a diverse tumor panel in sarcoma; there are so many diverse diseases within this sarcoma label, that the more we sequence these tumors and the more we learn about the nuances of all of them, the more it will help guide treatment.

We are in the infancy of the field right now and the more we learn, the more we will be able to forge forward. Hopefully, we will find a target and a drug will be developed. The only way we are going to learn is by doing.

Tawbi H A, Burgess MA, Crowley J, et al. “Safety and efficacy of PD-1 blockade using pembrolizumab in patients with advanced soft tissue (STS) and bone sarcomas (BS): results of SARC028—a multicenter phase II study. J Clin Oncol. 2016;34 (suppl;abstr 11006).