Best Methods for ALK Screening in Non–Small-Cell Lung Cancer

Anaplastic lymphoma kinase gene fusion, known as ALK positivity, varies in prevalence in previous studies of non–small-cell lung cancer (NSCLC) patients based on the detection method used. A new study sheds light on the prevalence of this subtype, suggests best methods for screening, and confirms that ALK-positive lung tumors have a better prognosis than ALK-negative NSCLC.

In patients with mutated ALK, “the resultant activated ALK protein kinase is a clinically validated therapeutic target for treatment with ALK inhibitors, of which crizotinib is the first in class,” according to study authors led by Rolf A. Stahel, MD, of University Hospital Zurich in Switzerland. Both the prevalence and prognostic impact of ALK positivity has been debated in varying studies.

In the new study, researchers analyzed tissue from 1,281 patients with lung adenocarcinoma in the European Thoracic Oncology Platform Lungscape iBiobank. The study used both immunohistochemistry staining (IHC) and fluorescent in situ hybridization (FISH) to test for ALK. Most patients were diagnosed between 2003 and 2009, and most were observed for at least 3 years of follow-up.

ALK positivity was seen with IHC in 80 patients, for a prevalence of 6.2%. Of those, 28 patients were also ALK FISH positive, yielding a prevalence with that method of 2.2%. That meant FISH had a sensitivity of only 35%, though that rose to 81.3% for IHC results of 2+ or 3+; the corresponding specificity was 99%. The authors wrote that because of the high specificity of FISH, it is reasonable to consider IHC-negative samples as also FISH-negative.

ALK IHC-positive patients were more frequently never-smokers, at 28.8% vs 18.4% of ALK IHC-negative patients (P = .017). Overall survival (OS) of patients differed significantly by ALK status, with a hazard ratio for survival for ALK-positive patients of 0.61 (95% CI, 0.41-0.90; P = .12). Relapse-free survival also was better in ALK-positive patients, with an HR of 0.65 (95% CI, 0.46-0.93; P = .018). The median OS was not reached in ALK-positive patients, compared with 69.5 months for ALK-negative patients.

Stahel said in an email that this study “gives further evidence that screening for ALK positivity and confirming by FISH would be an efficient way to identify patients for treatment with an ALK inhibitor. Patients with curatively resected ALK-positive tumors have a better prognosis than patients with ALK-negative tumors,” he added. “This has implications when designing adjuvant trials.”