The following is a summary of “Impact of Concurrent Genomic Alterations on Clinical Outcomes in Patients With ALK-Rearranged NSCLC,” published in the January 2024  issue of Oncology by Mejía et al.

ALK tyrosine kinase drugs have shown promise in fighting advanced NSCLC with ALK rearrangement. However, simultaneous DNA changes, like CDKN2A/B or TP53, may make specific treatments less effective. 

For a study, researchers sought to look at next-generation sequencing data from 116 patients with advanced ALK-rearranged non small cell lung cancer (NSCLC) from five cancer sites in Latin America from December 2017 to December 2022. Clinicopathologic and molecular traits were linked to clinical results and the risk of brain metastasis (BrM) in both individuals with and without physical changes happening at the same time. 

A second-generation ALK tyrosine kinase inhibitor was given to all 116 patients, and alectinib was chosen in 87.2% of cases. 62% of the cases had alterations. TP53 mutations (27% of the cases) and CDKN2A/B loss (18% of the cases) were the most common. Loss of CDKN2A/B was linked to a higher chance of BrM, with a total frequency of 33.3% compared to 7.4% in the subgroup that wasn’t changed. Patients who lost both CDKN2A and B at the same time (n = 21) had shorter median progression-free survival (10.2 mo vs. 34.2 mo, P < 0.001) and overall survival (26.2 mo vs. 80.7 mo, P < 0.001). 

In the multivariate study, losing both CDKN2A and B was linked to worse progression-free survival and overall survival, even when other somatic changes like TP53 mutations, BrM, and Eastern Cooperative Oncology Group Performance Status were also present. This study supported the worse predictive value, which showed changes that happened at the same time in people with ALK rearrangement. Loss of CDKN2A/B was strongly linked to worse results and a higher chance of brain tumors. Patients with ALK-positive tumors may be better chosen for more aggressive treatment and closer brain follow-up based on the results of their study.

Source: sciencedirect.com/science/article/abs/pii/S155608642300727X