Early Diagnosis and Treatment Are Critical in Achieving the Best Outcomes in Sarcoma

Vigilant screening practices, establishing an early diagnosis, and collaboration with a multidisciplinary treatment team are all key factors in the treatment of patients with rare cancers such as sarcoma, according to Breelyn Wilky, MD.

“Patients [with sarcoma] are often the healthiest and the strongest when they’re newly diagnosed, but if we don’t see them early, they may miss out on opportunities to participate in those early-line clinical trials,” Wilky explained. “This points to [the importance of] early referral and early input that we can have for patients so that they know all of their options as they’re making decisions.”

The most recent FDA approval in the sarcoma field was for afamitresgene autoleucel (Tecelra), which earned accelerated approval for the treatment of adult patients with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices.1 The approval of the MAGE-A4-directed genetically modified autologous T-cell immunotherapy was supported by findings from cohort 1 of the phase 1 SPEARHEAD-1 study (NCT03132922). Findings from the trial demonstrated that patients with synovial sarcoma who received a single infusion of the agent (n = 44) achieved an overall response rate per RECIST 1.1 criteria of 43.2% (95% CI, 28.4%- 59.0%), with a median time to response of 4.9 weeks (95% CI, 4.4-8.0) and a median duration of response of 6 months (95% CI, 4.6-not reached).

In an interview with OncLive, Wilky, the director of Sarcoma Medical Oncology, the Cheryl Bennett and McNeilly Family Endowed Chair in Sarcoma Research, and the deputy associate director for Clinical Research at the University of Colorado Cancer Center in Aurora, discussed various factors related to sarcoma diagnosis, management, and approaches to screening for the disease.

OncLive: How does lack of awareness for rare cancers affect patient care?

Wilky: Rare cancers are problematic for several reasons. Even getting the right diagnosis can be a challenge because oftentimes sarcoma, for example, is not at the top of someone’s differential when [a patient] presents with a mass in their arm or leg, which is a very common presentation for these types of diseases. Much more common [conditions] such as a lipoma or a cyst are often assumed to be the etiology, so the idea of getting an MRI or doing a biopsy may not come to the top of anyone’s list, so you wind up getting a late diagnosis.

That speaks to the awareness piece. [We need to] broadly communicate with patients across the country that there’s [a disease] called sarcoma and if you have a lump or a bump that’s bigger than a golf ball, then you need to think about this rare cancer called sarcoma.

What should community providers be aware of in the early stages of diagnosis of rare malignancies such as sarcomas?

Sarcomas can present anywhere, head to toe, and that’s a big challenge. If you’re a patient and you have a mass in an arm or a leg, then you might be able to feel it and notice it, whereas if it’s somewhere deep in the belly cavity or in the chest, it might not get found until fairly late when it starts to cause symptoms.

For community providers, a large mass is almost never a normal thing in an arm or a leg or on the trunk. At minimum, getting imaging early, before sending someone to a surgeon, is probably the most critical thing that changes outcomes. Our approach to everything from surgery to even potentially chemotherapy or radiation prior to attempting a surgery for these tumors drives survival and it drives the best outcomes. Getting that early diagnosis and having experts weigh in on that treatment plan is critical for patients to do the best they can.

What is the role of a multidisciplinary team in providing this kind of comprehensive care?

This is one of the pinnacles, [one of] the foundations of good sarcoma care. When you talk to folks who specialize in these diseases, it takes a village to take care of these patients. In our multidisciplinary clinic that we run every week at the University of Colorado, there are 30 [individuals] in the room. We have surgeons, and [among] surgeons, we have orthopedic oncologists who specialize in operating on arms, legs, and trunks. Then we have surgical oncologists who specialize in operating inside of the belly cavity, pelvis, [and other areas with] more visceral or organ involvement.

We have medical oncologists who focus on chemotherapy, but not just traditional chemotherapy. We use traditional chemotherapy, targeted therapies, and immune therapies now, all within the realm of our toolbox for the treatments that we’re offering patients. We have a pathologist who sorts out among 100 different types of sarcomas what type of sarcoma the patient has. That can be changed approximately 20% to 30% of the time when it comes to an expert bone and soft tissue pathologist from a community pathology interpretation. Sometimes that involves advanced genetic analysis to home in on the type of cancer that we’re dealing with.

Then we have radiologists who specialize in interpreting scans to help tell us whether this is likely to be a sarcoma or something more benign. It really does take a village of [specialists] who weigh in on treatments. When a patient comes in, they may meet with 2 or 3 different doctors—a surgeon, a radiation oncologist, and myself—and leave with a multimodal treatment plan moving forward.

What upcoming initiatives in sarcoma are you most excited for?

We always say, when in doubt, cut it out for sarcoma, and that’s the way we cure patients, [by] having their sarcoma completely removed with surgery or with a combination of radiation and surgery, or chemotherapy, radiation, and surgery. [However], a lot of our patients unfortunately present with sarcoma that’s already spread to other organs and it’s very difficult to cure patients with the same chemotherapy drug, doxorubicin, that we’ve used since the 1970s as the standard of care [SOC].

Much of what our research is focused on is improving the activity of those drugs. We have clinical trials for many different types of sarcomas, and we have them for patients who are candidates for chemotherapy or targeted therapies that are coming down the pipeline. Our research is focused not only on big trials, where new drugs that have been developed by companies are being tested to try to get approved. We’ve taken part in several clinical trials leading to new drugs that have gone on the market now for certain types of sarcomas.

What I’m excited about are the trials where we’re taking the SOC chemotherapy drugs and combining them with something else to make them [more effective]. One example is with doxorubicin. I’ve been running a clinical trial here for newly diagnosed patients with sarcoma, where doxorubicin is combined with 2 immunotherapy drugs that are designed to boost the immune system to fight the cancer. At first glance, that may sound crazy, because people always think of chemotherapy as suppressing our immune system. [However], when chemotherapy is first administered, it creates a very strong danger signal where your immune system tries to repair that damage that comes from chemotherapy. So, boosting the immune system at that key time we believe can help create longer memory in getting [the patient’s] whole body involved in fighting against this [disease].

Another [study is examining] gemcitabine and docetaxel. One of my colleagues at Washington University has developed a metabolic therapy that’s designed to starve the cancer while you’re giving chemotherapy and, through a complicated mechanism [of action], makes the chemotherapy work much better. We are one of only a few centers that’s participating in this clinical trial for patients with leiomyosarcoma, and translating the work that’s being done in laboratories into the clinic for our patients.

What is your primary message to your colleagues practicing in the community regarding sarcoma treatment?

The first message [is the importance of] early diagnosis and referral. There is nothing that says a patient can’t come have a second opinion at our multidisciplinary center. We’re a sarcoma center of excellence, which is based on volume. We see over 300 new patients with sarcoma every year, and that number is only growing. We are more than thrilled to work with our community partners and come up with a comprehensive [treatment] plan, and then we work with them to deliver that care for the patient closer to their home, if needed. They don’t have to be treated here in Denver, it’s more [about] getting that expert opinion on what the best course of action is for that patient.

The second piece is that clinical trials are not necessarily for when everything else has failed. [For example], the 2 trials I mentioned are early-line clinical trials, which means patients who are newly diagnosed can participate in a clinical trial that is not just [administering] the SOC. [These trials] are trying to make the SOC better.

Reference

FDA grants accelerated approval to afamitresgene autoleucel for unresectable or metastatic synovial sarcoma. FDA. August 2, 2024. Accessed January 14, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-afamitresgene-autoleucel-unresectable-or-metastatic-synovial-sarcoma