Retrospective Observational Study of ALK-Inhibitor Therapy Sequencing and Outcomes in Patients with ALK-Positive Non-small Cell Lung Cancer

Abstract

Background Data are sparse concerning the sequential use of multiple anaplastic lymphoma kinase (ALK) inhibitors for ALK-positive locally advanced or metastatic non-small cell lung cancer (NSCLC). Objective This study investigated sequencing and outcomes among patients receiving multiple ALK inhibitors. Patients and Methods This was a retrospective observational cohort study of adult patients with ALK-positive NSCLC treated with available first- and second-generation ALK inhibitors from 1 September 2011 to 31 December 2017. Duration of therapy (DOT) and overall survival (OS) were assessed with the Kaplan–Meier method. A multivariable linear regression analysis was performed to assess if DOT with a preceding ALK inhibitor was predictive of DOT for subsequent ALK inhibitor treatments. Results A total of 410 patients were analyzed: 57% received 1 ALK inhibitor; 35%, 2 ALK inhibitors; and 8%, 3–4 ALK inhibitors. Among those receiving > 1 ALK inhibitor ( n = 177), 60% received a crizotinib-led sequence and 39% an alectinib-led sequence. Nearly 60% of the overall population received chemotherapy prior to their first ALK inhibitor. Median OS for the study population was 28 months, 15 months in patients who received 1 ALK inhibitor, 42 months in patients who received 2 ALK inhibitors, and 56 months in patients who received 3–4 ALK inhibitors. Longer DOT of the first ALK inhibitor was associated with increased DOT of the second ( p < 0.0001), and longer DOT of the second ALK inhibitor was associated with increased DOT of the third ( p < 0.0001). Conclusions This study provides initial information on real-world treatment patterns following the introduction of new ALK inhibitors, and supports the use of sequential ALK therapies.

Feasibility and Challenges for Sequential Treatments in ALK-Rearranged Non-Small-Cell Lung Cancer

“…Sequential administration of effective drugs is critical in order to maximize therapeutic benefit and the survival of patients with NSCLC, main focus of previous studies has been the efficacy rather than the feasibility of therapeutic sequencing (8,(16)(17)(18)(19). Systematic analysis of the latter is endowed with serious difficulties, mainly the rarity and generally better prognosis of + NSCLC, the analysis regarding chemotherapy was performed in the subset of deceased patients (n=74, Figure 1), for which the entire disease trajectory could be studied.…”

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.…”

“…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. Among the latter, 14 studies used medical/health records only [ 29 , 33 , 34 , 37 , 41 , 43 , 46 , 47 , 48 , 49 , 51 , 52 , 53 , 54 ], four were based on administrative/claim data [ 31 , 38 , 39 , 40 ], and one study used data from cancer registries ( Table 1 ) [ 27 ]. Four studies [ 30 , 44 , 45 , 50 ] linked administrative/claim data with cancer registries.…”

Bioinformatics Analysis Predicts hsa_circ_0026337/miR-197-3p as a Potential Oncogenic ceRNA Network for Non-Small Cell Lung Cancers

“…These ndings indicated that circRNAs are closely related to the occurrence and development of diseases and maybe a potential target for the future diagnosis and treatment of the disease. However, most of the studies on circular RNA and non-small cell lung describe only a few genes description, and the mechanism of systematic molecular regulation is yet to be elucidated [21][22].…”