Abstract:
In 2021, the US Food and Drug Administration (FDA) approved two drugs targeting exon 20 directly: amivantamab and mobocertinib, under the accelerated approval pathway, for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy. Here we discuss questions regarding the core question of an \"unmet need\" within the accelerated approval pathway, contending that equipoise remain between the new compounds and previously existing options. Second, the NCCN\'s guidelines are currently recommending to sequence both drugs, a recommendation that is not based on any data. Last, post-marketing requirements may not shed clarity in the setting of these approvals. Our analysis has implications beyond patients with exon 20 insertion. In an era with growing identification of new and rarer molecular entities, misguided incorporation of new compounds into practice may obstruct trial enrollment in decisive clinical trials.
摘要:
2021年,美国食品和药物管理局(FDA)批准了两种直接靶向外显子20的药物:amivantamab和mobocertinib,在加速审批的路径下,对于患有表皮生长因子受体(EGFR)外显子20插入突变的局部晚期或转移性非小细胞肺癌(NSCLC)的成人患者,其疾病在铂类化疗后或后进展。在这里,我们讨论关于加速批准途径中“未满足的需求”的核心问题,主张在新化合物和以前存在的选项之间保持均衡。第二,NCCN的指南目前建议对两种药物进行排序,不基于任何数据的建议。最后,在这些批准的设置中,上市后的要求可能不会变得清晰。我们的分析具有超出插入外显子20的患者的意义。在一个越来越多的新的和罕见的分子实体识别的时代,错误地将新化合物纳入实践可能会阻碍决定性临床试验的试验纳入.