Background: Sequential treatment with first-, second-generation ALK TKI followed by third-generation TKI (lorlatinib) have been widely applied to ALK-positive lung cancer. However, acquired resistance is often driven by secondary ALK mutations, which are needed to be further explored. Circulating tumor DNA, a non-invasive approach, can detect tumor-derived DNA from multiple metastatic sites and has become a promising strategy for assessing the genetic evolution of tumors and analyzing TKI resistance. Conclusions: Genotyping of sequential post-progression plasma specimens reveals that treatment with sequential first-, second-, and third-generation ALK inhibitors can accelerate the accumulation of ALK resistance mutations and may lead to treatment-refractory compound ALK mutations. The selection for optimal first-line TKI is very important to achieve a more efficacious long-term strategy and prevent the emergence of on-target resistance. READ ARTICLE
Journal of Clinical Oncology DOI:10.1200/JCO.2021.39.15_suppl.3011
Authors: Gang Hua, Xiaoxi Chen, Ruoying Yu, Hua Bao, Xue Wu, Yang Shao
