WASHINGTON -- Sunitinib, an agent approved for use in several cancers, provides unprecedented antitumor activity in thymic carcinoma, a rare but aggressive tumor of the thymus gland, according to a phase II clinical trial led by a researcher at Georgetown Lombardi Comprehensive Cancer Center.
The study's results, published in Lancet Oncology, are the first to demonstrate a robust response in patients who had failed chemotherapy, the standard treatment for this cancer, says the study's senior investigator, Giuseppe Giaccone, MD, PhD, associate director for clinical research at Georgetown Lombardi.
"Disease control was achieved in over 90 percent of patients tested," says Giaccone. "This represents a significant advance in the care of these patients. More than half of the 24 patients who participated had failed two or more prior treatments."
Preliminary data from this study was presented at the 2014 annual meeting of the American Society of Clinical Oncology.
The median progression-free survival was seven-plus months, he added. Approximately 60 percent of patients were alive 18 months after treatment.
The research team included investigators from the National Cancer Institute, a part of the National Institutes of Health (NIH), Walter Reed National Military Medical Center and Indiana University Medical Center.
Investigators also tested sunitinib in 16 patients with thymoma, a less aggressive form of cancer in the organ, but the agent doesn't show much activity, according to Giaccone.
Sunitinib has a number of targets that are involved in angiogenesis, such as VEGFR and PDGFRb. Growth of these vessels may play an important role in the aggressiveness of thymic carcinoma. Sunitinib was the first cancer drug simultaneously approved (in 2006) for two different indications -- renal cell carcinoma and resistant gastrointestinal stromal tumor.
The scientists also found that sunitinib increases expression of a surface protein known as programmed cell death protein 1 (PD-1) in regulatory T cells, which was linked to longer survival. For this reason, Giaccone is planning a clinical trial to test a PD-1 antibody in patients with thymic carcinomas.
"Our research demonstrated why sunitinib is beneficial in thymic carcinoma, while also uncovering an approach that may offer even better results," Giaccone says. "Recently, remarkable activity has been observed in several solid tumors with antibodies that target PD-1 or its ligand PDL-1, including renal cell cancer, melanoma and non-small cell lung cancer."
This research was supported by the Intramural Research Program of the NIH, National Cancer Institute's Center for Cancer Research, and Cancer Therapy Evaluation Program (CTEP). Sunitinib was provided by Pfizer and distributed by CTEP.
Researchers who participated in the study include: Yisong Wang, PhD, from Georgetown Lombardi; Anish Thomas, MD, Arun Rajan, MD, Arlene Berman, RN, Udayan Guha, MD, PhD, Yusuke Tomita, MD, PhD, Min-Jung Lee, PhD, Sunmin Lee, MS, Jane B. Trepel, Eva Szabo, MD, Alexander Ling, MD, and Paul Meltzer, MD from the National Cancer Institute; Christina Brzezniak, MD, and Corey A. Carter, MD, from the Walter Reed National Military Medical Center; Aaron J. Spittler, RN, and Patrick J. Loehrer, MD, from Indiana University Medical Center; and Seth M. Steinberg, PhD, from the NIH.
Giaccone reports having no personal financial interests related to the study.
About Georgetown Lombardi Comprehensive Cancer Center
Georgetown Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and MedStar Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Georgetown Lombardi is one of only 41 comprehensive cancer centers in the nation, as designated by the National Cancer Institute (grant #P30 CA051008), and the only one in the Washington, DC area. For more information, go to http://lombardi.georgetown.edu.
About Georgetown University Medical Center
Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis - or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization (BGRO), which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health.
The Lancet Oncology