According to results from a retrospective study presented by Vineeth Tatineni, MD, Department of Medicine, Summa Health, Akron, Ohio, et al at the virtual 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, newer generations of ALK inhibitors demonstrated improved survival and blood-brain barrier penetration in non-small-cell lung cancer (NSCLC) with brain metastases. 

“First-generation ALK inhibitors have restricted efficacy due to blood-brain barrier penetration and ALK-resistant tumor mutations. Second-generation ALK inhibitors have shown better blood-brain barrier penetration, while third-generation ALK inhibitors were efficacious even against ALK-resistant mutations,” explained Dr Tatineni and colleagues.

Researchers investigated overall survival (OS) and progression-free survival (PFS) in NSCLC with brain metastases patients treated with first, second, and third-generation ALK inhibitors. The Cox proportional model estimated the OS and PFS, OS, was defined as the start date of systemic therapy to the final follow-up or death date. 

The data analyzed from patients included molecular marker status, systemic therapies, and date of progression; evaluation occurred between 2010 and 2019. 

A total of 90 patients had ALK gene rearrangement with 16 ALK+ patients received crizotinib, a first-generation inhibitor, while 17 received either second-generation (alectinib, ceritinib, brigatinib) or third-generation ALK inhibitors (lorlatinib),

In the first-generation cohort, the respective 5-year OS and PFS were 49% (95% CI, 24%,71%) and 43% (95% CI, 19%, 65%), while the median PFS was 45.3 months. Meanwhile, in the second and third-generation cohort, the 5-year respective OS and PFS were 76% (95% CI, 40%, 92%; P= 0.019) and 72% (95% CI,42%,89%) and the median PFS was 180.1 months.

“We determined that there was a significant 5-year OS benefit in patients who received second and third-generation ALK inhibitors compared to first-generation ALK inhibitors, and a respective trend towards significant PFS benefit in newer-generation ALK inhibitors when compared to first-generation,” concluded Dr Tatineni et al. 

Tatineni V, O'Shae PJ, Rauf Y. Outcomes of first, second, and third-generation anaplastic lymphoma kinase (ALK) inhibitors in non-small cell lung cancer brain metastases (NSCLCBM). Presented at: the 2021 ASCO Annual Meeting; June 4-8, 2021; virtual. Abstract 2034.—Alexandra Graziano