Ribeiro Maurício Fernando Silva Almeida, Knebel Franciele Hinterholz, Bettoni Fabiana, Saddi Rodrigo, Sacardo Karina Perez, Canedo Felipe Sales Nogueira Amorim, Alessi João Victor Machado, Shimada Andrea Kazumi, Marin José Flávio Gomes, Camargo Anamaria Aranha, Katz Artur
Oncology Center, Hospital Sírio-Libanês, Rua Dona Adma Jafet, 91, 01308-050, São Paulo, SP, Brazil.
Molecular Oncology Center, Hospital Sírio-Libanês, Rua Dona Adma Jafet, 91, 01308-050, São Paulo, SP, Brazil.
NPJ Precis Oncol. 2021 Feb 12;5(1):5. doi: 10.1038/s41698-021-00149-4.
The survival outcomes of the FLAURA trial support osimertinib as the new standard of care for untreated patients harboring activating mutations in the epidermal growth factor receptor (EGFR). Despite the initial response, disease progression invariably occurs. Although uncommon, BRAF V600E mutation arises as a unique mechanism of resistance, and thus far, no prospective studies are available to support concurrent EGFR/BRAF blockade. We report a case of impressive radiological and ctDNA response under dabrafenib, trametinib, and osimertinib in an advanced EGFR-mutant lung adenocarcinoma patient who developed BRAF V600E as one of the acquired resistance mechanisms to second-line osimertinib. Moreover, the patient experienced remarkable clinical improvement and good tolerance to combination therapy. The present case suggests the importance of prospective studies evaluating both efficacy and safety of the combination in later line settings and points towards the potential of ctDNA to monitor resistance mechanisms and treatment benefit in clinical practice.
FLAURA试验的生存结果支持奥希替尼作为表皮生长因子受体（EGFR）激活突变的未治疗患者的新护理标准。尽管有初始反应，但疾病进展总是会发生。BRAF V600E突变虽然不常见，但却是一种独特的耐药机制，迄今为止，尚无前瞻性研究支持同时进行EGFR/BRAF阻断。我们报告了一例晚期EGFR突变肺腺癌患者，该患者在接受二线奥希替尼治疗时出现BRAF V600E作为获得性耐药机制之一，在使用达拉非尼、曲美替尼和奥希替尼联合治疗后出现了令人印象深刻的影像学和循环肿瘤DNA（ctDNA）反应。此外，该患者临床症状显著改善，对联合治疗耐受性良好。本病例表明，开展前瞻性研究评估联合治疗在后续治疗中的疗效和安全性具有重要意义，并指出ctDNA在临床实践中监测耐药机制和治疗获益的潜力。
