A new oral combination therapy shows promise in slowing the progression of advanced leiomyosarcoma, a relatively uncommon type of soft tissue cancer. Findings from a recent study published in The Lancet Oncology suggest that the combination of cabozantinib and temozolomide may offer a valuable treatment option for patients with this challenging disease.
Leiomyosarcoma originates in the smooth muscle tissue, and can develop in various parts of the body, including the digestive system, blood vessels, and uterus. It’s characterized by its potential for rapid growth and spread. Currently, standard treatment for advanced leiomyosarcoma typically involves systemic therapies, including chemotherapy regimens like doxorubicin, gemcitabine, trabectedin, and pazopanib.
Despite these treatments, many patients eventually experience disease progression. The average survival rate for advanced leiomyosarcoma is approximately two years, underscoring the critical need for more effective therapeutic strategies.
The study investigated whether combining cabozantinib, a tyrosine kinase inhibitor, with the oral chemotherapy drug temozolomide could improve outcomes. Cabozantinib works by inhibiting pathways crucial for tumor growth and blood vessel formation, specifically targeting the VEGF receptor, which is often overexpressed in sarcoma cells. Temozolomide is already a component of standard sarcoma treatment and can be administered over extended periods.
“Prior evidence suggested that combining anti-angiogenic therapies with chemotherapy could have complementary effects,” explains Dr. Seth Pollack, the Steven T. Rosen, MD, Professor of Cancer Biology at Northwestern University, and a co-author of the study. “The goal of this study was to determine whether an all-oral combination regimen could provide meaningful disease control for patients with advanced leiomyosarcoma who had already received multiple prior treatments.”
The research involved 72 patients with unresectable or metastatic leiomyosarcoma and other soft tissue sarcomas who had previously undergone treatment. Participants received oral cabozantinib (40 milligrams) daily, along with temozolomide (150 milligrams/m2) for the first five days of a 28-day cycle. In the second cycle, the temozolomide dosage was increased to 200 milligrams/m2 for the same five-day period.
The primary measure of success was progression-free survival at 12 weeks. The results showed that 74 percent of patients who continued receiving the cabozantinib and temozolomide combination achieved this milestone. Importantly, the treatment was generally well-tolerated, with no treatment-related deaths reported.
“Side effects were consistent with what is known about these drugs, most commonly involving low blood counts, along with manageable non-hematologic effects such as high blood pressure and diarrhea in a smaller number of patients,” Dr. Pollack noted.
These findings suggest that the combination of cabozantinib and temozolomide holds potential as a treatment option for patients with advanced leiomyosarcoma. The study’s results support further investigation into this therapeutic approach.
Northwestern Medicine is actively pursuing additional research avenues for leiomyosarcoma. Dr. Pollack and his team are currently conducting a clinical trial evaluating zanzalitinib, a single-agent tyrosine kinase inhibitor, as a potential treatment.
“Together, these efforts reflect a broader strategy to expand and improve treatment options for patients with advanced leiomyosarcoma through thoughtfully designed clinical trials,” Dr. Pollack stated.
This research was supported by Exelixis.
Northwestern Medicine, in partnership with Siemens Healthineers, is also advancing precision care through innovation in imaging, theranostics, interventional radiology, and radiation oncology. This collaboration aims to establish a global center of excellence in theranostics, a personalized approach to cancer diagnosis and treatment using radiopharmaceuticals. Northwestern Medicine is recognized as a leader in quality healthcare, pioneering treatments and breakthrough discoveries, including a novel approach to repairing damaged donor lungs, resulting in the hospital performing more lung transplants than any other U.S. Hospital last year.
The institution also offers advanced treatments for other complex conditions, such as a rare liver transplant for a patient after lung cancer and a fertility-sparing procedure for a patient with rectal cancer. Northwestern Medicine continues to invest in medical breakthroughs and access to care initiatives, including a first-of-its-kind program in Illinois offering pregnancy support for women with higher BMIs.
