Georgetown University. US: 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.