Christina T. Loguidice
Thymic carcinomas are extremely rare and aggressive tumors. According to the American Cancer Society, they occur at a rate of 1.5 cases per every million people in the United States, which works out to approximately 400 new diagnoses annually.1
Because these tumors are so uncommon, it has been difficult to compare treatments to determine the best approach to care after platinum-based chemotherapy fails. Now, a study recently published in Lancet Oncology
has shown that sunitinib, an orally administered tyrosine kinase inhibitor approved by the US Food and Drug Administration for use in renal cell carcinoma and resistant gastrointestinal stromal tumors, provides unprecedented antitumor activity in thymic carcinoma.2
This finding was observed in an open-label phase 2 clinical trial that included 39 assessable patients (41 were enrolled but two were excluded due to ineligibility and death) with histologically confirmed chemotherapy-refractory thymic epithelial tumors (25 thymic carcinomas and 16 thymomas). All patients received 50 mg of sunitinib orally once daily, which was administered in 6-week cycles, with 4 weeks of treatment followed by 2 weeks without treatment until tumor progression or unacceptable toxicity. The median follow-up was 17 months.
Of the 23 assessable patients with thymic carcinomas, six (26%) had partial responses, 15 (65%) achieved stable disease, and two (9%) had progressive disease. Of the 16 patients with thymomas, one (6%) had a partial response, 12 (75%) had stable disease, and three (19%) had progressive disease.
“Disease control was achieved in over 90% of [thymic carcinoma] patients tested,” said the study’s senior investigator Giuseppe Giaccone, MD, PhD, associate director for clinical research, Georgetown Lombardi Comprehensive Cancer Center, in a press release.3
“This represents a significant advance in the care of these patients,” he added, while noting that sunitinib did not show much activity in thymomas.
Treatment with sunitinib was generally well tolerated by the study participants. The most common grade 3 and 4 treatment-related adverse events were lymphocytopenia, fatigue, and oral mucositis, each of which affected eight patients (20%). There were also five patients (13%) who experienced decreases in left-ventricular ejection fraction, of which three (8%) were grade 3 events. There were three deaths (8%) during the study, including one resulting from a cardiac arrest that was likely related to treatment.
Sunitinib is known to target a number of processes involved in angiogenesis, and Dr Giaccone and researchers also found the agent to increase the expression of a surface protein known as programmed cell death protein-1
) in regulatory T cells, which was linked to longer survival. Based on this finding, Dr 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,” said Dr Giaccone. “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.”
The study was funded by the National Cancer Institute’s Cancer Therapy Evaluation Program.
1. American Cancer Society. What are the key statistics about thymus cancers? http://www.cancer.org/cancer/thymuscancer/detailedguide/thymus-cancer-key-statistics
. Last Revised January 28, 2015. Accessed February 23, 2015.
2. Thomas A, Rajan A, Berman A, et al. Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial. Lancet Oncol
3. FDA approved drug extends survival for patients with rare cancer [news release]. Washington, DC: Georgetown University Medical Center; January 12, 2015. http://gumc.georgetown.edu/news/FDA-Approved-Drug-Extends-Survival-Patients-Rare-Cancer.
Accessed February 23, 2015.