Advances Continue in Sarcoma Care, Offer Blueprint for Other Tumor Types

George D. Demetri, MD

Advancements in sarcoma are both revolutionizing the treatment of this heterogeneous disease and influencing the research and treatment approach in other tumor types, according to George D. Demetri, MD.

The field of sarcoma has had a leading role in the reclassification of cancers into numerous subtypes and individualized treatment approach to these subtypes. Epigenetic advances in sarcoma are also leading the way for other tumor types.

OncLive: What recent research have you found to potentially be practice-changing in the treatment of sarcomas?

In an interview with OncLive, Demetri, senior vice president for Experimental Therapeutics at the Dana-Farber Cancer Institute, professor of Medicine at Harvard Medical School, and codirector of the Ludwig Center at Harvard, discusses current trends in sarcoma care, how the field of sarcoma has paved the way for other tumor types, and emerging therapeutic advances in the field.Demetri: Interestingly, at the 2016 AACR Annual Meeting, there was not a lot that was practice-changing. There was a lot that was practice-informing; and a lot of the changes in practice, such as the introduction of immuno-oncology to a variety of solid tumors, have already changed practice.

What we’re seeing now is more evidence—hard evidence, longer-term outcomes about why that change in practice was absolutely required. These things are expensive; we have to watch the cost of these drugs and the way we take care of people. However, on the other hand, they are magnificent in their activity, and they are probably only going to get better. We are probably at “version 1.1” of immuno-oncology. On my Mac, I’m on version 10 of the operating system. We are going to get that kind of improvement as we go forward.

In our world of sarcomas, there has not really been anything practice-changing. What we’re seeing is a coalescing of the continuum of science: from the most basic discovery scientists, who deal with worms and basic mechanisms of DNA and enzymes, all the way up to the most clinical of clinicians. This includes our colleagues in the pediatric oncology world, where pediatric sarcomas are a prevalent population. We have many more adult sarcoma patients but, proportionally, there are a lot of pediatric sarcoma experts who are really looking to move that science into the clinic for pediatrics. We are trying very hard to make that a true continuum between the basic scientists and clinical scientists, and the pediatric and adult oncologists.

How has the evolution of sarcoma research impacted oncology as a whole?

The changes in practice could not have happened without the advances in basic science. That’s why we need that kind of public investment for the unfettered curiosity of these scientists who I respect, and then the practicality of the academic investigators and the industrialists who are really trying to derive it to practice-changing methods.Sarcoma, which is near and dear to my heart, continues to pave the way for what we are seeing in every other type of cancer. This is the parsing of all cancers into lots of different kinds. There must be 100 to 500 different kinds of sarcomas. We are seeing that come up in lung cancer, breast cancer, and colorectal cancer. This is not a one-size-fits-all disease. We are even seeing some cancers be decommissioned; a certain thyroid cancer recently got decommissioned and researchers said, “No, this is not a cancer at all.”

How have you seen the therapies in this field advance?

Sarcoma has taught us a lot about how powerful words are. The diagnoses drive the way people treat them. By giving them more defined and precise diagnoses, we can then match the clinical trials and the options for therapy to a more precise group of patients. Sarcoma has really led the way that we’re seeing now in all other cancers.In our world of sarcomas, we’re seeing that same kind of convergence. We are seeing targeted therapies take off. The first proof-of-concept of TRK inhibitors was in a patient with sarcoma who had a TRK fusion. Those are things we knew would happen, and they are having a reality check in real-world efficacy data from some of our clinical trials.

We haven’t seen much yet about the immuno-oncology space; there will be more of that at the 2016 ASCO Annual Meeting from our group and other groups. There will be good opportunities there, just as there are in every other field of medicine.

What are your thoughts on the affinity enhanced T-cell therapy that has shown early—but significant—promise?

The other place sarcoma is really leading the way is in the epigenetic space. The data on malignant rhabdoid sarcomas, epithelial sarcomas, and synovial sarcomas are going to lead the way with EZH2 inhibitors and other epigenetic drugs.Yes, there is the recent breakthrough therapy designation of the engineered T-cell therapy with the technology that comes out of a publically funded science at the NCI; that has now been taken into the company Adaptimmune. That’s very exciting work in synovial sarcoma.

Really, that is just the tip of the iceberg because you can engineer and optimize a T cell to recognize almost anything you want. Therefore, the fact that we are going after NY-ESO-1—something that is highly expressed on synovial sarcoma—is really just a big toe in the water. We are getting into this field of what our institution now is starting to call the “cellular pharmacy”—the idea that we are using living drugs rather than just static drugs that we just pull off of the shelves.