Coalterations in ALK-Positive Patients Affect Efficacy of Targeted Therapies

Worse clinical outcomes and higher risk for brain metastasis are more likely to happen in patients with metastatic ALK-rearranged non-small cell lung cancer (NSCLC) who also have co-occurring genetic alterations compared with patients who do not harbor coalterations.

These are the findings of Luis Lara-Mejia, MD, and colleagues, who conducted a study that analyzed next-generation sequencing data of 116 patients from five Latin American cancer centers. Their goal was to determine if co-occurring genetic alterations negatively affect the efficacy of ALK-targeted therapies.

Coalterations were seen in 62% of patients, and the two most common were TP53 mutations (27%) and CDKN2A/B loss (18%). All patients received a second-generation ALK tyrosine kinase inhibitor, with the majority (87.2%) receiving alectinib (Alecensa).

ALK-positive patients who also had CDKN2A/B loss had a shorter median progression-free survival compared with patients without coalterations (10.2 vs 34.2 months, respectively). Moreover, median overall survival (OS) was also worse for these patients (26.2 vs 80.7 months, respectively).

In addition, there was an increased risk of brain metastasis in patients with CDKN2A/B loss (33.3%) versus patients without coalterations (7.4%).

The researchers hope their findings will shed light on patients with ALK-positive NSCLC tumors and may result in closer brain follow-up during treatment.