Identifying a patient's genetic mutation led University of Arkansas for Medical Sciences (UAMS) physician-researcher Ling Gao, M.D., Ph.D., to an existing drug that eliminated the patient's stage IV Merkel-cell carcinoma. Gao's findings, made in collaboration with two other UAMS researchers, were published today in The New England Journal of Medicine.
Metastatic Merkel-cell carcinoma is often fatal and there is no effective treatment. Gao's 86-year-old female patient was diagnosed in 2013 with stage IIIB Merkel-cell carcinoma of the right temple. She had surgery and received radiation therapy in May 2013 and additional surgery in July 2014. In November 2014, doctors confirmed that the cancer had metastasized.
Gao, a dermatologist who treats Merkel-cell carcinoma patients from Arkansas and surrounding states, performed genetics tests on the tumor that revealed multiple mutations, including PI3Kδ.
Gao was aware that the drug idelalisib is a novel PI3K pathway inhibitor approved by the Food and Drug Administration (FDA) for treatment of B-cell lymphoma, a cancer of the blood. She was also aware of recent studies showing that disruption of the PI3Kδ mutation allows the body to mount an effective antitumor immune response.
On the basis of her laboratory work and knowledge of idelalisb, Gao began treatment of the patient with the drug on Feb. 6, 2015. Her findings were published in the Journal in a letter to the editor.
Three months after administering the idelalisib, there was no sign of the tumor in the patient's liver, Gao said
Based on what she's learned, Gao said the case can be made for further study of PI3Kδ inhibitors like idelalisib in solid tumors, not just blood cancers.
"The efficacy of idelalisib in our patient provides initial clinical evidence that the targeting of PI3Kδ in Merkel-cell carcinoma is warranted," Gao said in the letter, which
was also signed by UAMS' Fade Mahmoud, M.D., and Mallory B. Shiver, M.D.
University of Arkansas for Medical Sciences