Everolimus/vemurafenib

Abstract

Skin rash, otalgia and erythematous rash: 2 case reports In a investigator-initiated, nonrandomized, open-label, dose-escalation phase 1 clinical trial (NCT01596140) consisting of 5 patients, two patients were described: A 10-year-old boy developed skin rash during treatment with vemurafenib and everolimus while a 22-year-old man developed otalgia and erythematous rash during treatment with vemurafenib [not all routes and outcomes stated; time to reaction onsets not stated]. A 10-year-old boy, who had WHO grade II pleomorphic xanthoastrocytoma of the left inferior parietal lobe, had previously been treated with focal proton therapy and two surgical resections. He was found to have a BRAFV600E alteration. Therefore, he started receiving vemurafenib 480mg twice a day and oral everolimus 2.5mg daily. Subsequently, his tumour decreased. However, he developed grade 3 skin rash secondary to vemurafenib and everolimus. Therefore, vemurafenib and everolimus were discontinued for 10 days. The rash improved with unspecified supportive measures. Vemurafenib and everolimus were reinitiated. At last followup, he was in partial remission in cycle 41 of vemurafenib and everolimus. No further toxicity was noted. A 22-year-old man, who had initially been diagnosed with a right temporal WHO grade III anaplastic astrocytoma, had been treated with subtotal resection, focal radiation therapy and temozolomide. Subsequently, local progression with WHO grade IV glioblastoma was noted. He was treated with subtotal resection, temozolomide, veliparib, carmustine and isotretinoin [13-cisretinoic acid]. BRAFV600E mutation was identified on molecular profiling. Therefore, he started receiving vemurafenib 960mg twice a day. However, he developed severe otalgia and erythematous rash secondary to vemurafenib. Therefore, vemurafenib dose was decreased to 720mg twice a day. He remained stable on this regimen for 13 months until disease progression. Following disease progression, he was treated with vemurafenib along with everolimus for 4 months until further disease progression.