Dramatic response induced by vemurafenib in a BRAF V600E-mutated lung adenocarcinoma.

Case Report A 66-year-old man, a never-smoker, was referred to our oncology department in April 2011 for stage IV non–small-cell lung cancer (NSCLC). The patient had developed progressive left thoracic pain followed by dyspnea and fatigue. A subsequent chest computed tomography (CT) scan showed massive left pleural effusion and pleural thickening, mainly involving the mediastinal pleura. Histologic examination of pleural biopsies revealed poorly differentiated adenocarcinoma that was positive for CK7 and thyroid transcription factor 1 and negative for Wilms tumor 1 and calretinin. [F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scanning additionally showed intense metabolic activity in the left pleura and celiac lymph nodes. Brain magnetic resonance imaging was negative. Polymerase chain reaction (PCR) and pyrosequencing did not reveal any activating epidermal growth factor receptor (EGFR) mutation. Reverse transcriptase PCR did not show any specific ALK rearrangement. Given the patient’s never-smoker status, additional molecular analyses were performed and revealed a BRAF V600E mutation. The patient underwent left pleurodesis and subsequently completed four cycles of chemotherapy with cisplatin and pemetrexed, with a partial response. Eleven cycles of continuation maintenance chemotherapy with pemetrexed, with a nearly complete radiologic response, were delivered; however, PET/CT scanning in May 2012 showed progression in a single left pleural nodule and a left internal mammary lymph node, with high FDG uptake in both lesions. A left extrapleural pneumonectomy was discussed and performed in June 2012. Histologic examination showed a solid adenocarcinoma measuring 3 cm in largest diameter, with vascular invasion, positive resection margins in multiple pleural locations, and 14 metastatic lymph nodes, including six nonregional lymph nodes. The patient underwent hemithoracic external-beam radiotherapy with a total dose of 66 Gy encompassing all sites of incomplete tumor resection. After 10 sessions of radiotherapy at a dose of 2 Gy per day, and exactly 2 months after surgery, a follow-up CT scan revealed multiple new hepatic metastases involving both hepatic lobes (Fig 1). Off-label vemurafenib was started in September 2012 at a dose of 960 mg administered twice per day. Concurrent radiotherapy that was restricted to the location of the positive resection margins was resumed, using a schedule of seven daily doses of 3 Gy, for a local total dose of 51 Gy, to prevent local symptomatic chest wall recurrence. Within 2 weeks, the patient developed a grade 3 rash covering the entire previously irradiated field that was consistent with a strong photosensitizing effect associated with a recall-like phenomenon; the rash persisted for more than 4 weeks (Figs 2A and 2B). Follow-up CT scanning in September 2012 showed excellent partial response (Fig 3). PET/CT scanning in October 2012 after 6 weeks of treatment showed complete response, with no residual metabolic activity in the hepatic lesions (Fig 4). The patient is currently asymptomatic except for mild fatigue. During the third week of treatment, he developed common secondary skin lesions, such as keratoacanthoma, and treatment is ongoing under active surveillance.