George D. Demetri, MD
Soft tissue sarcoma is on the forefront of precision medicine, says George Demetri, MD, professor of Medicine at Harvard Medical School and director of the Center for Sarcoma and Bone Oncology at Dana-Farber Cancer Institute.
This is particularly evident by the FDA’s approval of eribulin mesylate (Halaven) in for advanced or unresectable liposarcoma, a relatively rare subtype of soft tissue sarcoma which affects approximately 4000 patients a year in the United States.
“It’s interesting that the FDA honed in on just liposarcoma. In some ways, that’s one of the most interesting things about this approval,” says Demetri. “Sarcomas, in many ways, set the stage for parsing cancers into very specific little bins.”
The approval was based on an improvement in overall survival (OS) demonstrated in a phase III study that looked at patients with either liposarcoma or leiomyosarcoma following prior treatment with an anthracycline-based chemotherapy.
In the 143 patients with liposarcoma, eribulin demonstrated a median OS of 15.6 months compared with 8.4 months in those who received dacarbazine (HR, 0.51; 95% CI, 0.35-0.75). Median progression-free survival (PFS) with eribulin was 2.9 versus 1.7 months with dacarbazine (HR, 0.52; 95% CI, 0.35-0.78).
An OS benefit was not reported in the 309 patients with leiomyosarcoma.
In an interview with OncLive
, Demetri discusses the study, the impact of the eribulin’s FDA approval, what oncologists can learn from studying liposarcoma, and the challenges that come with treating a rare disease.
OncLive: What is the significance of the eribulin approval?
: The FDA approved this drug in 2010—a long time ago—for patients with breast cancer. Therefore, it is already kind of an older drug. This is a second indication—a supplementary indication in the liposarcoma world.
It’s very interesting because, at the 2015 ASCO Annual Meeting, the study that had it registered by the FDA in sarcomas was presented as a leiomyosarcoma and liposarcoma study. There are several reasonably common types of sarcomas: GIST, which is the most common type, the gastrointestinal stromal tumor, and then leiomyosarcomas and liposarcomas.
Now, their biology is totally different. They simply both start with L. That is what they share. That’s about it. What’s interesting is that the study was really the first randomized prospective study showing that people could live longer if they were treated with a chemotherapy drug. All of the other studies that have been done have never really proven that in any of the soft tissue sarcomas, other than GIST. That is an important consideration.
When the FDA looked at eribulin compared with the older standard drug, dacarbazine— which is from the 1970s—there was not that much of a difference in leiomyosarcomas. However, there was a much bigger difference in liposarcomas favoring the newer eribulin. That is why the FDA approved it for liposarcomas. It is interesting that the liposarcomas were so positive that it drove the whole benefit, despite the fact that there was not an incremental benefit in the leiomyosarcomas.
When you mix it all together, the whole study was positive; that tells you just how statistically positive it was for the liposarcomas.
How will this approval change the treatment paradigm for liposarcoma?
This approval helps to dispel some of the nihilism that exists in the field of sarcomas. Although they are hard to treat we now have better tools and new drugs to treat them with, and it’s worth thinking about.
Many practicing oncologists may only see 1 of these sarcoma patients every decade. That is a message that I think we need to get out there. Even though these are rare diseases, the standards of practice and the options for patients are changing because of good precision medicine research. I think that’s important.
What should oncologists know about using eribulin to treat liposarcoma?
Every oncologist knows the side effects of eribulin because everybody has used it for patients with breast cancer. It has standard chemotherapy side effects: low blood counts, hair loss, and the risk of neuropathy. Eribulin, if given for too long, can damage nerves, so that is something every oncologist knows to look out for.
Eribulin has a survival benefit, so we should always think about that in people with liposarcoma. It is a modest survival benefit, so that’s the other important thing to know.