Oncotarget: Anaplastic lymphoma kinase rearrangement and non-small cell lung cancer

Oncotarget published "Anaplastic lymphoma kinase rearrangement prevalence in patients with advanced non-small cell lung cancer in the United States: retrospective real world data" which reported that rearrangement prevalence was assessed overall and then stratified by patient characteristics. The overall ALK rearrangement prevalence was 2.6%.

Differences in ALK status also varied by age and race, with young patients having a higher prevalence vs. older patients; Asian patients had a prevalence of 6.3%.

Patients that were positive for other mutations or rearrangements had a lower ALK positivity rate and patients positive for PD-L1 had a rate of 3.0%.

The likelihood of finding an ALK translocation was highest in younger patients and nonsmokers; however, age and smoking history were not discriminative enough to exclude testing based on clinical variables.

Age and smoking history were not discriminative enough to exclude testing based on clinical variables

Dr. Eric H. Bernicker from The Houston Methodist Hospital said, "The ability to detect actionable alterations in patients with advanced lung cancer has revolutionized the field of thoracic oncology and is in part responsible for a significant decline in mortality."

However, uptake of routine testing as per NCCN guidelines has been slow for a variety of reasons, including small biopsies, tissue exhaustion from sequential testing and slow diffusion of knowledge.

Timely identification of patients who might benefit from tyrosine kinase inhibitors is crucial, as it is known that TKIs selected on the basis of a driver alteration gives patients a much better chance at prolonged response rather than getting treatment following systemic chemotherapy.

Responding patients often have prolonged non-trivial survival benefit—a recent study found a median OS of 48 months in a cohort of patients treated mostly with an older generation of ALK TKIs.

Figure 2: Prevalence of ALK rearrangement in aNSCLC patients by histology type and smoking status.

Clinical predictors, while useful, have been recognized for a long time as being insufficient for deciding which patients with advanced pulmonary adenocarcinoma should be tested.

These authors performed a retrospective study of a database to acquire real-world clinical data on the frequency of the translocation in a large pool of patients drawn primarily from community hospitals and practices.

The Bernicker Research Team concluded in their Oncotarget Research Output, "this retrospective review of nearly 20,000 patients with aNSCLC and tested for ALK in the United States confirms that ALK rearrangements are found more commonly in younger nonsmokers and patients of Asian descent. We did not observe a significant difference in prevalence between males and females. However, a substantial minority of cases are found across all age groups, in patients with a history of smoking as well as patients with squamous histology and no history of smoking. Our findings strongly reinforce the need for earlier broad gene panel testing in all patients with advanced lung non-squamous aNSCLC regardless of clinical features. This approach has the potential to identify the maximum number of patients who could benefit from correct identification of actionable driver alterations, ultimately providing these patients with the maximum benefit of molecular therapeutic regimes."

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DOI - https://doi.org/10.18632/oncotarget.28114

Correspondence to - Eric H. Bernicker - bernicker@houstonmethodist.org

Keywords - ALK rearrangement, NSCLC, prevalence

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