BRAF V600E Inhibition in Anaplastic Thyroid Cancer

Abstract

T h e ne w e ngl a nd jou r na l o f m e dicine n engl j med 368;7 nejm.org february 14, 2013 684 with the information necessary to identify the affected products (assuming that the company knew where all the devices were shipped). How-ever, as our article stated, only a small number of each type of device was being recalled. The prob-lem for the health care community is not only knowing which devices are being recalled, but also knowing whether the affected product was ever received, finding the affected product among a much larger (unaffected) group of devices, and determining whether any of the recalled devices had been used — and if so, in which patients. Most hospitals and other organizations have not sufficiently invested in their own infrastructure to be able to efficiently and effectively determine specifically which devices they have, which they have used, and (through an electronic-health-record or other clinical-information system) whether any of the recalled devices had been used in patients. The UDI system is intended, among other things, to facilitate the develop-ment of such capabilities. To the Editor: Anaplastic thyroid cancer is a rare, highly virulent malignant condition that is associated with a median survival of only 5 months despite the best multidisciplinary care. BRAF is a serine-or threonine-specific protein kinase in the mitogen-activated protein kinase pathway, which regulates cell division and survival. The activating mutant protein BRAF V600E is detected in cutaneous melanoma, classic hairy-cell leuke-mia, papillary thyroid cancer, and about one quarter of anaplastic thyroid cancers. 1,2 The BRAF inhibitor vemurafenib (PLX4032) improves survival among patients with metastatic mela-noma 3 and induces a response in patients with hairy-cell leukemia. 4 In a mouse model, the BRAF inhibitor PLX4720 suppressed growth of mutated human anaplastic thyroid cancer. 5 We describe a dramatic response to vemu-rafenib in a 51-year-old man with BRAF-mutated anaplastic thyroid cancer. He had a 1-month history of enlarging neck masses, hoarseness, dysphagia, and dyspnea. Thyroid masses and jugulodigastric lymphadenopathy were detected on physical examination, and unilateral vocal-cord paralysis and diffuse supraglottic edema were detected by means of direct laryngoscopy. On day 1, hypermetabolic thyroid masses; neck, mediastinal, and pulmonary hilar lymphadenop-athy; and lung and bone lesions were detected by means of 18 F-fluorodeoxyglucose–positron-emis-sion tomography (18 F-FDG–PET) and computed tomography (CT). Thyroidectomy and tracheos-tomy were performed on day 2; anaplastic thy-roid cancer associated with papillary cancer was diagnosed. On days 4 and 10, low, radiosensitizing pacli-taxel (at a dose of 45 mg per square meter of body-surface area) and carboplatin (at an area under the curve of 2) were administered. How-ever, the patient had progressive dyspnea, and 60 to 100% inspired oxygen was administered through the tracheostomy to maintain pulse-oximetry readings of 92 to 94%, so he was moved to an intensive care unit. CT showed worsening pulmonary infiltrates and nodules. Vemurafenib at a dose of 960 mg orally twice daily was started empirically on day 10 with the patient's consent. His condition improved rap-idly, radiation therapy to the neck and upper mediastinum was started on day 14, and he was discharged from the hospital on day 16 while receiving vemurafenib. Results of tumor analysis by means of real-time polymerase-chain-reaction assay later showed the BRAF T1799A (V600E) mutation. 18 F-FDG–PET and CT of the chest on day 38 showed nearly complete clearing of meta-static disease (Fig. 1). This case suggests the benefit of BRAF inhi-bition in anaplastic thyroid cancer with activat-ing BRAF mutations. Observations in more patients will be required to determine the fre-quency and durability of responses, mechanisms