Can We Extend Beyond 2 Years of Adjuvant ALK TKI Established by ALINA and ELEVATE in Resected Early Stage ALK+ NSCLC a Disease with High Predilection for CNS Metastasis with Novel Clinical Trial Designs?

The development and approval of three generations of ALK tyrosine kinase inhibitors (TKIs) since the identification of anaplastic lymphoma kinase fusions (ALK+) in NSCLC has led to improved survival especially with lorlatinib, the only third-generation ALK TKI in the metastatic incurable stage. The establishment of 3 years of adjuvant EGFR TKI in resected stage IB-IIIA EGFR+ NSCLC has led to improvement in overall survival (OS) when compared to placebo. Logically, the use of adjuvant ALK TKI in resected early-stage ALK+ NSCLC has been investigated. But instead of three years of adjuvant TKI, in line with EGFR+ and RET+ NSCLC, the use of ALK TKI was investigated for only 2 years in both ALINA and ELEVATE trials. Unsurprisingly, alectinib (ALINA trial) and ensartinib (ELEVATE trial), respectively, has led to improved disease-free survival (DFS) so far with OS follow up on-going. Nonetheless, this is a disease that requires constant tumor suppression to prevent or delay CNS metastasis, as exemplified by the CNS data from the 7-year CROWN update. In addition, to reviewing the results of ALINA and ELEVATE, we propose two alternate novel clinical designs to build upon the 2-years of adjuvant 2G ALK TKIs.