Existing drug extends survival for patients with rare thymic carcinoma

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 published in Lancet Oncology (2015; doi:10.1016/S1470-2045(14)71181-7).

The study's results are the first to demonstrate a robust response in patients who had failed chemotherapy, the standard treatment for this cancer, said the study's senior investigator, Giuseppe Giaccone, MD, PhD, associate director for clinical research at Georgetown Lombardi Comprehensive Cancer Center in Washington, DC.

"Disease control was achieved in over 90% of patients tested," said 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 ASCO annual meeting.

The median progression-free survival was 7-plus months, he added. Approximately 60% 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 the surface protein 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 said. "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."

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