Afatinib, an irreversible ErbB family blocker, with protracted temozolomide in recurrent glioblastoma: A case report

作者：Alshami Jad; Guiot Marie Christine; Owen Scott; Kavan Petr; Gibson Neil; Solca Flavio; Cseh Agnieszka; Reardon David A; Muanza Thierry^*

来源：Oncotarget, 2015, 6(32): 34030-34037.

DOI：10.18632/oncotarget.5297

• afatinib
• temozolomide
• glioblastoma
• next-generation sequencing
• epidermal growth factor receptor

There are few effective treatments for recurrent glioblastoma multiforme (GBM). We present a patient with recurrent GBM who achieved a prolonged response to treatment with afatinib, an irreversible ErbB family blocker, plus temozolomide. A 58-year-old female patient was diagnosed with multifocal primary GBM. After surgical resection, first-line therapy comprised radiotherapy and temozolomide. Following disease progression after 3 temozolomide cycles, the patient entered a phase I/II clinical trial of afatinib (20-40 mg daily for 28 days) plus temozolomide (50 mg/m(2) every 21/28 days). Next-generation sequencing analysis of the brain tumor specimen was performed. At the last assessment, 63 treatment cycles had been completed and the patient had survived for similar to 5 years since recurrence. Significant disease regression was observed after 5 cycles and was maintained during long-term follow-up. Adverse events were consistent with the known tolerability profile of afatinib and were managed by treatment interruption/dose reduction. The patient had several epidermal growth factor receptor (EGFR) aberrations, including gene amplification and EGFRvIII positivity. Three somatic mutations were identified, including an unprecedented extracellular-domain substitution (D247Y). The patient has survived similar to 6-fold longer than normally expected in patients with recurrent GBM. The complex EGFR genotype may underlie sustained response to afatinib plus temozolomide.

• 出版日期2015-10-20
• 单位McGill