The US Food and Drug Administration (FDA) has approved a treatment for the first time for use in patients with Erdheim-Chester disease (ECD), a rare hematologic malignancy affecting about 600 to 700 patients worldwide. These patients have very limited life expectancy, the agency notes.
The approval is for use of the targeted therapy vemurafenib (Zelboraf, Genentech/Roche) in patients with ECD whose cancer cells have the BRAF V600 mutation (approximately 54% of patients).
Vemurafenib is already available for use in melanoma with BRAF V600 mutations.
“Today’s approval of Zelboraf for patients with ECD demonstrates how we can apply knowledge of the underlying genetic characteristics of certain malignancies to other cancers,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence. “This product was first approved in 2011 to treat certain patients with melanoma that harbor the BRAF V600E mutation, and we are now bringing the therapy to patients with a rare cancer with no approved therapies.”
In its announcement, the agency explains that ECD is a slow-growing blood cancer that originates in the bone marrow. ECD causes an increased production of histiocytes, a type of white blood cell. Excess histiocytes can result in tumors infiltrating many organs and tissues throughout the body, including the heart, lungs, and brain.
The approval, which has a breakthrough therapy designation, was based on efficacy results from the use of vemurafenib in 22 patients with BRAF V600 mutation–positive ECD. Half of these patients (11 of 22 [50%]) experienced a partial response and 1 patient (4.5%) experienced a complete response.
The median duration of response was not estimable at a median follow-up time of 26.6 months, the manufacturer noted.
These data were collected as part of the phase 2 VE-BASKET study, which was conducted in patients with a variety of cancers and other diseases testing positive for BRAF V600 mutations. Basket studies use an innovative clinical trial design that matches a disease’s underlying genetic profile to the mechanism of action of the medicine, instead of enrolling people primarily on the basis of their disease or its location, the company explained.
Common side effects of vemurafenib reported in these patients with ECD included arthralgia, maculopapular rash, alopecia, fatigue, prolonged QT interval, and papilloma.
Previously reported severe side effects of vemurafenib include the development of new cancers (skin cancer, squamous cell carcinoma, or other cancers), growth of tumors in patients with BRAF wild-type melanoma, hypersensitivity reactions (anaphylaxis and drug reaction with eosinophilia and systemic symptoms [DRESS] syndrome), severe skin reactions (Stevens-Johnson Syndrome and toxic epidermal necrolysis), heart abnormalities (QT prolongation), hepatotoxicity, photosensitivity, severe reactions in the eye (uveitis), immune reactions after receipt of radiation treatment (radiation sensitization and radiation recall), kidney failure, and thickening of tissue in the hands and feet (Dupuytren’s contracture and plantar fascial fibromatosis).
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