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

Abstract

Background. Little is known about real-world treatment and outcomes of patients with anaplastic lymphoma kinasepositive (ALK+) advanced non-small cell lung cancer (NSCLC). Patients 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, through 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 post crizotinib (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 post crizotinib (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 AE SE, 1.976 AE 0.112; p < .0001). Conclusion. Median rwPFS in patients with advanced ALK+ NSCLC was < 8 months for firstand 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. The Oncologist 2020;25:867-877 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.

Heterogeneous Tumor-Immune Microenvironments between Primary and Metastatic Tumors in a Patient with ALK Rearrangement-Positive Large Cell Neuroendocrine Carcinoma

“…ALK rearrangement is most commonly seen in lung adenocarcinoma [ 7 , 25 ]. ALK-TKIs have dramatically improved overall response rates in NSCLC with ALK rearrangement in clinical trials relative to conventional chemotherapy [ 26 , 27 ]. However, patients eventually develop disease progression because of acquired resistance through various mechanisms, resulting in treatment failure [ 25 , 26 ].…”

“…ALK-TKIs have dramatically improved overall response rates in NSCLC with ALK rearrangement in clinical trials relative to conventional chemotherapy [ 26 , 27 ]. However, patients eventually develop disease progression because of acquired resistance through various mechanisms, resulting in treatment failure [ 25 , 26 ]. Additionally, patients with brain metastasis of ALK rearrangement-positive NSCLC have been known to have shorter progression-free survival (PFS).…”

“…ALK rearrangement-positive tumors are at high risk of relapse and patients with ALK rearrangement-positive tumors usually develop disease progression because of acquired resistance [ 26 ]. In addition, LCNEC has a generally poor prognosis similar to small-cell lung cancer [ 10 ].…”

Real-World Utilization of Target- and Immunotherapies for Lung Cancer: A Scoping Review of Studies Based on Routinely Collected Electronic Healthcare Data

“…Screening of titles and abstracts allowed the selection of 131 potentially eligible studies. Among them, a total of 32 studies fulfilled the eligibility criteria and were finally included into the review [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. No further studies were retrieved through a snowballing search.…”

“…Twenty-six out of 32 included studies used rcEHD from North America [ 27 , 28 , 29 , 30 , 31 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ], two studies used data from Asia [ 24 , 32 ], three from Europe [ 26 , 42 , 55 ], and one from Australia [ 25 ]. Thirteen studies used record linkage of ≥1 type of data source [ 24 , 25 , 26 , 28 , 30 , 32 , 35 , 36 , 42 , 44 , 45 , 50 , 55 ], while 19 studies were based on one data source type only.…”