Osteosarcoma: Leading-Edge Insights and Personalized Care
Summary
- Dr. Emanuela Palmerini is using genetic and immune signatures to advance more precise treatment strategies for osteosarcoma.
- Only one new drug has been approved for osteosarcoma in the past several decades, mifamurtide. Dr. Palmerini’s studies focus on finding the cancer signatures linked to better response to mifamurtide.
- Dr. Palmerini’s research into molecular signatures of sarcomas could one day tailor treatment to each patient’s biology instead of a one-size-fits-all approach.
With rare cancers like osteosarcoma, the greatest challenge is the lack of tailored treatment options. For children and young adults facing this aggressive bone cancer, treatments have hardly changed in decades.
Emanuela Palmerini, M.D., Ph.D., has built her career around finding ways to improve care.
Two recent papers, published in the Journal of Clinical Oncology and Clinical Cancer Research, respectively, showcase Dr. Palmerini’s work using genetic and immune signatures to advance more precise treatment strategies for osteosarcoma.
What is Osteosarcoma?
Osteosarcoma is the most common bone cancer in children and young adults. But it is rare, with only about 800 cases a year in the U.S. Treatment is long and toxic. The standard chemotherapy for osteosarcoma comes with significant short- and long-term side effects.
“Suddenly, a 20-year-old is no longer in school but spending nine months in treatment,” Dr. Palmerini said. “We need to use the best tools we have. These tumors are very aggressive and, when they come back after initial treatment, there are very, very few therapeutic options.”
Dr. Palmerini, a sarcoma researcher at Sylvester Comprehensive Cancer Center, part of University of Miami Miller School of Medicine, and professor in the Division of Medical Oncology, has dedicated her career to improving outcomes for kids and young adults with osteosarcoma.
She relocated to Miami this spring after more than 20 years at the Rizzoli Orthopedic Institute in Bologna, Italy. Her goal here is to find new treatment options for these cancers and deepen her international ties, an essential element in rare cancer research.
Her leadership in the international GRACefUl Project has revealed major survival differences among ultra-rare sarcoma subtypes. At the same time, as co-chair of FOSTER (Fight OsteoSarcoma Through European Research), she directs Europe-wide trials to accelerate osteosarcoma drug discovery.
Refining Osteosarcoma Treatment
Only one new drug has been approved for osteosarcoma in the past several decades, mifamurtide. It works by stimulating the immune system and is approved only in Europe, where it is often added to chemotherapy.
Even so, researchers weren’t sure which patients actually benefited from it. Dr. Palmerini’s studies focused on finding the cancer signatures linked to better response to mifamurtide. She hopes to tailor treatment so that only those most likely to benefit receive it, sparing some patients months of side effects.
These tumors are very aggressive and, when they come back after initial treatment, there are very, very few therapeutic options…My hope is that we find better drugs and I think it’s possible.
Dr. Emanuela Palmerini
In the Journal of Clinical Oncology clinical trial, the researchers studied the benefit of mifamurtide for high-grade osteosarcomas that haven’t spread but were at a higher risk of relapse because their cancers had ABCB1/P-glycoprotein, which pumps chemotherapy drugs out of the cell.
Patients who received mifamurtide and chemotherapy were less likely to have cancer grow, spread or come back, particularly for high-risk patients. However, other factors may be at play in who benefits from mifamurtide.
The Clinical Cancer Research study explored how the immune cells and signals around a tumor affect treatment response.
“There are factors in the tumor microenvironment that are protective,” Dr. Palmerini said. “Others are harmful.”
The researchers identified two important genetic “signatures” in the tumor’s immune environment. They linked the first, a 21-gene signature, to protective microenvironment signatures and improved survival. Patients with this signature were at lower risk, with a five-year overall survival of 92%, compared to high-risk patients with a five-year survival of 47%. The second, a 31-gene signature, indicates that patients are most likely to benefit from mifamurtide.
Personalized Medicine: Hope in Tailored Treatment
Dr. Palmerini’s research into molecular signatures of sarcomas could one day tailor treatment to each patient’s biology instead of a one-size-fits-all approach. At Sylvester, she sees the early signs of this approach highlighted in the phase 1 clinical trials program at the new Kenneth C. Griffin Cancer Research Building.
Some of these trials test brand-new drugs for the very first time. Others are basket trials that group patients with shared characteristics, regardless of where the cancer started. An osteosarcoma tumor with the same mutation as a breast cancer may potentially benefit from the same treatment.
For rare tumors like sarcomas, these basket trials open the door to leading-edge drugs. These trials allow Sylvester patients access to promising therapies “that may not otherwise be available for sarcoma,” Dr. Palmerini said. “It’s very exciting because, in orphan diseases like sarcoma, you have the possibility to offer patients a second chance.”
That’s why early referral to a dedicated sarcoma center like Sylvester is critical, Dr. Palmerini said. Timely diagnosis and expert care can mean the difference between a cure and the cancer spreading. Despite the challenges, she remains optimistic.
“My hope is that we find better drugs,” she said, “and I think it’s possible.”
Tags: cancer research, chemotherapy, clinical trials, Dr. Emanuela Palmerini, osteosarcoma, sarcoma, Sylvester Comprehensive Cancer Center