Real-World Treatment Patterns and Progression-Free Survival Associated With Anaplastic Lymphoma Kinase (ALK) Tyrosine Kinase Inhibitor Therapies for ALK+ Non-Small Cell Lung Cancer

Background: Little is known about real-world treatment and outcomes of patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC).

Materials and methods: This retrospective study of the Flatiron Health EHR-derived deidentified database included patients with a lung cancer diagnosis and confirmed advanced NSCLC who received ALK tyrosine kinase inhibitor (TKI) therapy (January 1, 2011, to June 30, 2018). Patient characteristics and treatment patterns were characterized. Real-world progression-free survival (rwPFS) and time to discontinuation were calculated using the Kaplan-Meier method.

Results: First-line ALK TKI therapy was administered to 581 patients (27.5% had brain metastasis on or prior to initiation) and second-line ALK TKI therapy to 254 patients postcrizotinib (45.7% had brain metastasis on or prior to second-line ALK TKI initiation). Crizotinib (84.6%; n = 492) was the most commonly administered first-line ALK TKI therapy. For second-line ALK TKI postcrizotinib (n = 254), 49.6% received ceritinib, 41.7% received alectinib, 5.9% received crizotinib retreatment, and 2.8% received brigatinib. Median (95% confidence interval [CI]) rwPFS was 7.47 (6.48-8.32) months for first-line and 7.30 (5.72-8.42) months for second-line ALK TKI. Median (95% CI) rwPFS was significantly longer among first-line ALK TKI patients without than with brain metastasis (8.52 [7.57-10.59] vs. 4.97 [3.75-5.99] months; p < .0001) and patients with brain metastasis on or prior to first-line ALK TKI therapy had a significantly increased risk of progression (hazard ratio ± SE, 1.976 ± 0.112; p < .0001).

Conclusion: Median rwPFS in patients with advanced ALK+ NSCLC was < 8 months for first- and second-line ALK TKI therapy and was even shorter in patients with brain metastasis, highlighting the need for more effective treatments in this patient population.

Implications for practice: Results presented herein describe real-world treatment of advanced ALK+ NSCLC with ALK TKI therapies from January 2011 through June 2018. Crizotinib was the most commonly prescribed first-line ALK TKI therapy in this patient population, but the majority of data analyzed were obtained prior to Food and Drug Administration approval of alectinib and ceritinib in the first-line ALK TKI setting. Physicians should monitor patients closely to help identify when a change in treatment should occur.

Related Products

Cat.No.	Product Name	Information
S1068	Crizotinib	Crizotinib is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM in cell-based assays, respectively. It is also a potent ROS1 inhibitor with Ki value less than 0.025 nM. Crizotinib induces autophagy through inhibition of the STAT3 pathway in multiple lung cancer cell lines.

Related Targets

Autophagy ROS1 c-Met ALK