Collaborative Effort Fuels Sarcoma Advancements

Article

Denise Reinke, MS, NP, discusses the Sarcoma Alliance for Research through Collaboration, as well as the challenges and up-and-coming advancements in sarcoma.

Denise Reinke, MS, NP

Scientific breakthroughs can be difficult in a rare disease such as sarcoma, which makes up less than 1% of all adult cancers and comprises more than 50 subtypes.

Pharmaceutical companies do not always want to invest in such a small market, and it can be difficult to even recruit enough patients to run an effective clinical trial.

The Sarcoma Alliance for Research through Collaboration (SARC) is working to change that, said Denise Reinke, MS, NP, president and CEO of the nonprofit organization.

“SARC was formed because a group of researchers and physicians—from both the clinic and the laboratory—realized that, if you want to make progress in a rare disease, you really need to pool your resources intellectually, as well as your patient and monetary resources to be as smart as possible in designing what needs to be done,” said Reinke.

The Ann Arbor, Michigan—based organization was created in 2003 by medical and pediatric sarcoma experts at 5 major medical facilities to conduct innovative sarcoma research dedicated to advancing the care of their patients. Today, they have a large presence in the sarcoma space—providing tools such as the SARC Biospecimen Bank, genomic data sets, and the sarcoma drug-response portal.

SARC also funds numerous researchers through grants and conducts clinical trials throughout the country. Currently, SARC has 11 active clinical trials, including a phase II study of pembrolizumab (Keytruda), which was the first investigator-led study of the anti—PD-1 agent to be conducted in advanced sarcoma. Interim results, which were presented at the 2016 ASCO Annual Meeting, demonstrated that pembrolizumab reduced tumor size in 33% of patients with undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.

OncLive: How does SARC find patients for clinical trials that focus on just a few subtypes in such a rare disease?

As subtyping becomes more common and other cancers are broken down into smaller groups, what can researchers studying other tumors learn from sarcoma?

To learn more about SARC as well as the challenges and up-and-coming advancements in sarcoma, OncLive spoke with Reinke who, in addition to her leadership role, has previously worked as a sarcoma nurse practitioner on clinical trials and within the pharmaceutical industry.Reinke: We bring together all the centers across the United States with sarcoma programs. It is mostly the larger centers that have dedicated sarcoma programs, so we try to have as much of a geographic reach as possible with our trials, so that patients have access and are not at a disadvantage because they don’t happen to live in a big city like Houston, Boston, or New York. We try to—as much as possible—have our trials open across the country so that patients who need these treatments have the best opportunity to be included.We joke, “welcome to our world,” as we have been working with small subtypes for a while. The collateral benefit of this is companies are now beginning to realize that this is an important space to explore and that sarcomas have an equal footing in the game. Maybe it’s not so much about where the cancer is anatomically, but what the genetic signature and footprint of it is. That can be across different types.

Have new technologies, such as next-generation sequencing, that help define different subtypes had an impact in the treatment of patients with sarcoma?

Our understanding of how to do this work in a small population and how to recruit that population can certainly be applied across other types of cancers.It still remains to be seen. The genetic profiles of all cancers tend to be complex and they don’t always just identity, “here is what is wrong and here is the drug against it that will give a patient benefit.”

It hasn’t turned out to be as clear-cut as we had hoped. It has helped us begin to understand some of the potential drivers and, hence, identify some potential treatments to target those drivers, but there is still a lot of work ahead. All of the incredible people working across all types of cancers continue to be perplexed and stumped by how to eradicate these diseases.

Interim data from the SARC-028 trial was just presented at the 2016 ASCO Annual Meeting, which showed a benefit of pembrolizumab for patients with undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. What is the significance of this trial?

However, we are making progress. Technology has helped us go from just looking grossly at a specimen under the microscope to really getting into the cellular level and understanding drivers.In general, it is an understood business principle that companies look for the largest potential market. Unfortunately, most of our diseases fall into smaller groups. Therefore, we were just so thrilled to have the opportunity to do an investigator-initiated and lead study of an immunotherapy in sarcoma.

Do you see immunotherapy continuing to be investigated in sarcoma?

There is just great promise for the potential of immunotherapy to help people with cancer. Given the age range of patients with sarcoma—which are aged from newborns all the way to young adults and from middle-aged to octogenarians—there is such a great potential to help people. We were thrilled to have the opportunity to do this trial.Absolutely. The fact that there was a signal with pembrolizumab in this population—especially with a single agent since we are moving to combinations in many other areas—is impressive. We had patients who were kind of enough to allow us to obtain biopsies and blood samples before and after exposure to the drug, and these should be helpful in getting us identify who may or may not benefit from this treatment.

What other trials or research areas is SARC involved in that should be highlighted?

Having that information, we might even be able to help patients across other subtypes of sarcoma that were not investigated in this trial. This pilot study has been incredibly beneficial in helping us to better understand the appropriate use of these therapies.We are currently involved in a study looking at overcoming resistance to gemcitabine using HDAC inhibitors. We often take agents that have been around for a while and have been a bit of an enigma, in terms of how best to use them in the armamentarium against cancer. We see if we can utilize them in sarcoma. There are a number of compounds that have been developed to overcome drug resistance, and we are really trying to exploit that and understand it better.

We are going to be moving forward with another immunotherapy study in sarcoma, which is looking at it in combination with radiation therapy. We want to see if we can enhance the benefits of radiation by utilizing immunotherapy.

Additionally, we continue to have a strong interest in malignant peripheral nerve sheath tumors, which is a very difficult subtype of sarcoma that occurs across a broad age range and is associated with neurofibromatosis.

Patients who have NF1 mutations have a higher risk of developing this aggressive, and often times lethal, form of sarcoma. We’ve been collaborating with researchers at the National Cancer Institute and there is a group within the Department of Defense that supports this type of research, specifically in this subtype of sarcoma, that we are collaborating with. We are going to be embarking on a fourth trial to try and move this field forward.

What sort of advancements do you see on the horizon in sarcoma?

There is another area SARC is particularly proud of and interested in continuing to pursue. In 2012, we were awarded a Sarcoma SPORE grant from the NCI. This year, we will be finishing up the fifth year of our grant and we are in the process of submitting a competitive renewal to hopefully continue that work. It is leveraging $2.3 million annually for 5 years to do this work. It is a huge contribution to the scientific community interested in sarcoma, and it has really been instrumental in moving the science forward.Immunotherapy has great potential. We also see biotech companies beginning to develop very targeted, specific compounds, which is a very exciting area. Instead of the broad cytotoxic chemotherapy—where you just go after everything and hope you kill it—we can target just the cancer and there are a lot less side effects. This is critical. The key is getting something that is beneficial as well as tolerable, because some of these patients are on these drugs for a long time.

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