Ortega-Franco Ana, Rafee Shereen
Experimental Cancer Medicine Team, The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester, M20 4BX, UK.
Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
Oncol Ther. 2022 Jun;10(1):13-22. doi: 10.1007/s40487-022-00190-8. Epub 2022 Mar 16.
The introduction of tyrosine kinase inhibitors (TKI) for the treatment of metastatic non-small cell lung cancer (NSCLC) harbouring sensitizing epidermal growth factor receptor (EGFR) gene mutations revolutionized the diagnostic and treatment algorithm of this subset of patients almost two decades ago. Since then, a number of trials have evaluated the role of TKI therapy in early-stage disease, with encouraging disease-free survival (DFS) results but lack of a survival advantage. ADAURA, a phase III trial evaluating 3 years of adjuvant osimertinib versus placebo in patients harbouring EGFR mutations with completely resected stage IB-IIIA NSCLC, recently reported a profound DFS benefit (hazard ratio 0.21), favourable quality of life and reduction in the risk of brain metastases. These results led to osimertinib's fast track approval by the US Food and Drug Administration, with this drug thus becoming the first EGFR-TKI approved for the treatment of early-stage disease. However, the key endpoint of overall survival remains immature and questions around indication (i.e. stage, need for adjuvant chemotherapy), optimal treatment duration, biomarkers of response and cost-effectiveness remain to be answered. In this article, we critically appraise the findings of ADAURA and discuss future challenges.
大约20年前，酪氨酸激酶抑制剂（TKI）被引入用于治疗携带敏感表皮生长因子受体（EGFR）基因突变的转移性非小细胞肺癌（NSCLC），这几乎彻底改变了这类患者的诊断和治疗方案。从那时起，多项试验评估了TKI疗法在早期疾病中的作用，虽然无病生存期（DFS）结果令人鼓舞，但缺乏生存优势。ADAURA是一项III期试验，评估了在完全切除的IB-IIIA期NSCLC且携带EGFR突变的患者中，3年辅助使用奥希替尼与安慰剂的疗效，最近报告了显著的DFS获益（风险比0.21）、良好的生活质量以及脑转移风险降低。这些结果导致奥希替尼获得美国食品药品监督管理局的快速批准，该药因此成为首个被批准用于治疗早期疾病的EGFR-TKI。然而，总生存这一关键终点仍不成熟，关于适应证（即分期、辅助化疗需求）、最佳治疗持续时间、反应生物标志物以及成本效益等问题仍有待解答。在本文中，我们对ADAURA的研究结果进行批判性评估，并讨论未来的挑战。
