Adding new monoclonal antibodies to chemotherapy improves survival in patients with soft tissue sarcoma

Adding new monoclonal antibodies to chemotherapy improves survival in patients with soft tissue sarcoma -

Added a new monoclonal antibody therapy to conventional chemotherapy increased the median survival of nearly a year in patients with advanced sarcoma stage cancer of the soft tissue lethal. The results of a multicenter clinical trial of combination therapy, conducted by researchers at Columbia University Medical Center and NewYork-Presbyterian, represent the first significant improvement in Kaposi's results for decades.

The study was published online earlier this month The Lancet

"We felt from preclinical data that the new drug -. Olaratumab - may improve survival in these patients by a few months, but the magnitude of improvement exceeded the expectations of everyone, "said Chief Gary K. Schwartz study, MD, professor of medicine at Columbia University Medical Center and chief of the division of hematology and oncology at NewYork-Presbyterian / Columbia. "While sarcoma remains a deadly disease, we are encouraged that we are on the right track and we hope to build on this progress . "

soft tissue sarcomas are a group of cancers that occur in fat, muscle, nerve, joint linings, blood vessels and other tissues that connect, support and surround the different structures of the body. There are more than 50 types of sarcomas of various soft tissues.

If caught early, sarcomas can be treated effectively with surgery. However, if the disease is spread, or metastasis, a chemotherapy treatment done relatively little to slow the progression of the disease or improve survival. The median duration of survival after the diagnosis of advanced disease is 12 to 16 months. In 2015, 12,000 people were diagnosed with sarcomas of soft tissue and 5,000 died from the disease, according to the American Cancer Society.

there

several years, Dr. Schwartz (then at the Memorial Sloan Kettering Cancer Center) reported that a cell surface receptor called growth receptor alpha platelet-derived factor (PDGFR-alpha) - found in many people with soft tissue sarcomas - seemed to play a key role in tumor growth in specific subtypes of soft tissue sarcomas. By blocking this receptor, it has been able to get the sarcoma cells stop growing in his laboratory.

Work closely with scientists from ImClone, since acquired by Eli Lilly and Company, he developed the clinical trial with the olaratumab agent, a human monoclonal antibody that blocks the PDGFR-alpha and disrupts this pathway, which is critical for the growth of sarcoma. The drug has also been shown to enhance the effects of standard chemotherapy called doxorubicin, which is commonly used in the treatment of sarcoma.

In a clinical trial phase 2, 133 patients with soft tissue sarcoma of metastases were given either doxorubicin or doxorubicin and olaratumab. The median overall survival of patients in the doxorubicin group was 14.7 months compared to 26.5 months in the doxorubicin-olaratumab group. Olaratumab addition to standard chemotherapy did not increase significantly the side effects of treatment.

"As an oncologist, I am ecstatic that the drug worked as well as it did," said Dr. Schwartz. "As a physician-scientist, however, I remain frustrated because we still do not know exactly why it worked as well as it did. It could have a direct effect of tumor cells, the tumor microenvironment (cells immediately around the tumor cells), or even immune cells. the future development of this drug will be helped to understand that. "

Dr. Schwartz and his colleagues are now studying other potential drug targets for stop the progression of soft tissue sarcomas. "Sarcomas are complex. It is, in fact, several receptors on the cell surface. PDGFR-alpha is just one of the receptors that are overexpressed on sarcoma cells. We now have some ideas on how to combine drugs blocking several types of these receptors, which are likely to be more effective than targeting a single type of receptor, "he said.

Eli Lilly recently completed a larger, phase 3 clinical trials olaratumab, which included some of the patients of Dr. Schwartz at Columbia / NewYork-Presbyterian. The results of the study has not been published yet. Meanwhile, the FDA granted priority review drugs as a potential treatment for advanced soft tissue sarcoma.