The State of the Sarcoma Treatment Landscape: Alexander Spira, MD, PhD, FACP, FASCO

Alexander Spira, MD, PhD, FACP, FASCO, medical oncologist at Virginia Cancer Specialists and chief scientific officer of NEXT Oncology, discusses why treatment advances in soft tissue sarcoma (STS) have lagged behind other solid tumors, the diagnostic and access challenges patients face, and the barriers to biomarker-driven therapy in this rare cancer in this interview with The American Journal of Managed Care^® (AJMC^®).

This interview has been lightly edited for clarity.

AJMC: Why have treatment advances in sarcoma lagged behind other solid tumors?

Spira: There are a couple of reasons why. First of all, the mainstay of treatment is still chemotherapy for most people, and chemotherapy has a modest improvement. There have been some improved drugs over the last couple of years, but they're not super effective, and they're kind of dancing around the extremes. There hasn't been really solid improvement with novel therapies. Part of this is due to the rarity. Part of it is that there are also very different sarcomas. There are a lot of different sarcoma subtypes.

For STS, the mainstay of treatment is still doxorubicin-based therapy, sometimes in combination with other drugs, such as ifosfamide, sometimes by itself, sometimes given with a drug called dacarbazine, sometimes given with a drug called trabectedin. It has modest outcomes, so modest benefit. After that, you're really kind of rearranging the deck chairs. There are not a lot of novel therapies.

Sometimes immunotherapy works, and it can work very well. But more commonly than not, it does not work super well. There are some targeted therapies as well, but admittedly they don't work super well. Sometimes we get very lucky, but most of the time we're still focusing on the same drugs that have been around for quite some time. They do work well in some of the subtypes. But the real issue is that sarcoma is really not 1 disease. It's really a basket of multiple diseases, and it's really hard to study because it's so many different diseases that are kind of lumped together. That's why.

Then immunotherapy, as you know, works well in some cancers and not other cancers as well. Just hard to predict for sure.

AJMC: Sarcoma is sometimes diagnosed later than other cancers. Is this a result of misdiagnosis?

Spira: It's not really a misdiagnosis per se. Sometimes it can take a little bit of a while because sarcoma is a cancer of the muscle. Somebody presents with a strained calf, a strained something, and people keep telling them things until it doesn't get better. So, you can have a very big sarcoma. I've had sarcomas present as big as 22 centimeters. It's easy to get to a very large-sized cancer.

AJMC: What are some of the biggest challenges patients face once sarcoma is identified?

Spira: Some of the biggest issues also are that it's hard to find physicians who are specialized. I subspecialize in this, and other people do subspecialize in this as well. But the real challenge that we have is finding those people, and not everybody wants to take care of it. Patients will have to find experts who are able to manage them, and that is sometimes very hard to do.

There are physicians who can manage these in the community; there's no doubt that they are. There are a lot of physicians who can manage this very, very well, and they do so. Sometimes they'll have challenges managing the subtypes, so I think it's important to have contacts. Even though I see a lot of sarcomas—I saw a really rare one the other day—it’s important to have contacts where you can actually send or ask questions to where you have specific “How would you treat this uber-rare sarcoma," so to speak.

Obviously, there's academic medical centers as well that are experts as well, but not every patient has this immediate availability. It's important to have those contacts. At the end of the day, it's important to have those contacts and know who to ask and how to integrate them into our clinical care. It's also important that the academic medical centers work with the community doctors, not just usurp those patients because, again, at the end of the day, most of us can treat these in a very similar manner. It's important that everybody work together in the best interest of their patients to have care close to home where possible. It's a yin and a yang, as I like to say.

AJMC: How does the rarity of sarcoma affect clinical trial design?

Spira: Sarcomas are incredibly rare. There are probably 10,000 cases a year, and you subdivide it among all the other types so it's hard to come up with a treatment paradigm. But they are very different diseases. There are some subtle differences, but because of the lack of improvement in treatments, as well as the fact that it's all these types, it does make it really hard to do any clinical trials.

AJMC: What is the current role of biomarker-driven therapy in sarcoma?

Spira: We're still not 100% there. There are biomarker-driven therapies, but they're still uber rare. We're not quite there where this is a mainstay. It should be done because we should be looking for things such as “microsatellite instability–high” as well as other rare mutations, but there are no approved therapies for biomarker-driven STS yet. Hopefully, there will be at some point, but all these patients should get full [next-generation sequencing] panels because you will pick up rare mutations that you could target or find them a clinical trial for, right?

AJMC: What gaps remain in physician access and willingness to treat sarcoma?

Spira: There are still big gaps in physicians willing to treat these patients because these are kind of the ones who, "I don't see. I don't know what to do." Sometimes it's hard to find experts who feel comfortable in treating them. As an oncologist, obviously, you need to get help when you need to get help, but we need to make sure patients have access to people who either can treat them on their own or know who to ask and work in a collaborative manner for our patients.