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Tumors from 73% of patients with advanced NSCLC were tested for ALK rearrangements in 2019.
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Approximately 3 weeks passed between NSCLC diagnosis and ALK test result.
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In 2019, FISH and NGS were used for 32% and 52% of ALK tests, respectively.
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25% of patients with ALK-positive NSCLC began systemic therapy before receiving ALK test result.
Abstract
Introduction
Patients with non–small-cell lung cancer (NSCLC) whose tumors harbor anaplastic lymphoma kinase (ALK) rearrangements can be treated with ALK tyrosine kinase inhibitors. We assessed real-world ALK biomarker testing and treatment patterns of patients with NSCLC in the United States.
Patients and Methods
Data were extracted from the Flatiron Health electronic health record-derived deidentified database for patients aged ≥18 years with stage IIIB or IV NSCLC and ≥2 clinic visits between January 2011 and December 2019.
Results
Among 60,025 eligible patients, tumors from 36,691 (61.1%) patients were tested for ALK rearrangements, and 1042 (2.8%) tested positive (ALK+). From 2011 to 2019, ALK testing rates increased from 33.1% to 73.0%; testing via fluorescence in situ hybridization declined from 68.3% to 32.1% while next-generation sequencing increased from <1% to 52.2%. Although tissue samples were more commonly used than blood (85.1% vs. 13.5% of tests), blood sample testing increased from 0.1% in 2011 to 28.2% in 2019. Median (interquartile range) time from diagnosis of advanced NSCLC to first ALK+ test result was 23 (13-43) days, including laboratory processing time of 9 (6-14) days. For the 24.7% of patients with an ALK+ test result who began treatment before receiving the positive result, chemotherapy was initiated most often overall until 2018 when immuno-oncology agents became most common.
Conclusion
Although ALK testing in NSCLC increased over time, testing rates among eligible patients did not reach 100% during the study period. Treatment decisions for some patients with NSCLC may have been made without important, guideline-recommended biomarker data.
Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT).
Clinicopathological and demographical characteristics of non-small cell lung cancer patients with ALK rearrangements: a systematic review and meta-analysis.
Clinicopathological and demographical characteristics of non-small cell lung cancer patients with ALK rearrangements: a systematic review and meta-analysis.
First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study.
Based on the demonstrated benefits of these therapies in patients with ALK-positive (ALK+) NSCLC, guidelines published by the National Comprehensive Cancer Network (NCCN) and others recommend tumor molecular testing for ALK rearrangements at time of initial diagnosis and prior to initiation of therapy.
Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.
ALK rearrangements can be detected using multiple types of molecular assays, including fluorescence in-situ hybridization (FISH), immunohistochemistry (IHC), reverse transcription-polymerase chain reaction (PCR), and next-generation sequencing (NGS).
FISH was the first widely deployed methodology to determine the presence of ALK gene rearrangement. The FDA-approved, ALK [D5F3] CDx IHC assay can also be used as diagnostic assay and does not require confirmation by FISH.
NGS allows for the simultaneous detection of multiple alterations in relevant cancer genes in a single test, and in some instances can be used to guide diagnosis and use of targeted treatments.
While targeted therapies have led to significant improvement in the management and prognosis of ALK+ NSCLC, acquired resistance to ALK TKIs is nearly inevitable. Between 2015 and 2016, immuno-oncology (IO) agents targeting programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) gained regulatory approval in the United States (US) for patients with advanced NSCLC whose tumors express PD-L1 and who have disease progression despite platinum-based chemotherapy or after progression on targeted therapy.
Subsequent studies showing poor response rates and toxicities associated with PD-1/PD-L1 inhibitor monotherapy and use in combination with ALK TKIs in patients with ALK+ NSCLC resulted in modifications of treatment guidelines and a requirement for negative ALK test results before first-line administration of IO agents.
Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.
EGFR mutations and ALK rearrangements are associated with low response rates to PD-1 pathway blockade in non-small cell lung cancer: a retrospective analysis.
With the ongoing development of effective therapies targeting specific biomarkers and advancements in biomarker detection technology, vigilance is required to monitor patterns in biomarker testing practices to reveal unmet needs and optimize treatment decisions. In the current study, we assessed real-world patterns of ALK testing in community practices in the US in patients with advanced NSCLC.
Patients and Methods
Data Source
This was a retrospective observational study that utilized Flatiron Health's nationwide longitudinal, demographically and geographically diverse, de-identified database comprising electronic health record (EHR) data from over 280 cancer clinics (approximately 800 sites of care).
Birnbaum B, Nussbaum N, Seidl-Rathkopf K, et al. Model-assisted cohort selection with bias analysis for generating large-scale cohorts from the EHR for oncology research. 2020;arXiv:2001.09765v1.
The de-identified patient-level data in the EHRs include structured data (eg, laboratory values and prescribed drugs) and unstructured data collected via technology-enabled chart abstraction from physicians’ notes and other unstructured documents (eg, biomarker reports). Data provided to third parties are de-identified, and provisions are in place to prevent re-identification and protect patient confidentiality. This study included data from January 1, 2011 through December 31, 2019.
Patient Population
Patients were included in the analysis if they met the following criteria: (1) age ≥18 years, (2) confirmed diagnosis of advanced NSCLC, defined as clinical stage IIIB or IV, and (3) ≥ 2 clinic visits within the Flatiron Network between January 1, 2011 and December 31, 2019. The majority of clinic visits were from the community setting.
Outcomes
Baseline Demographic and Clinical Characteristics
Patient demographic and clinical characteristics were summarized based on ALK testing status (performed or not performed) and ALK test result received (positive or negative).
ALK Testing Patterns
Assessments of ALK testing patterns included proportions of patients tested for ALK rearrangements, ALK testing methodologies, sample types used for ALK testing, and timing of ALK test, including the time from diagnosis of advanced NSCLC to obtaining the ALK test result, and laboratory processing time, defined as the period between the testing laboratory obtaining the test sample and providing a positive or negative ALK test result. A sensitivity analysis for the years 2016-2019 was conducted to account for changes in technology and testing practices over the study period (2011-2019).
Treatment Patterns Before and After ALK Test Results
Systemic treatments for patients who underwent ALK testing were evaluated to determine the proportion of patients who initiated treatment before an ALK+ test result was received, the treatment class(es) used during that period, line of treatment when the ALK+ test result was received, and treatment administered after the ALK+ test result was received. Assessment of PD-L1 testing patterns and timing of PD-L1 testing was also performed.
Statistical Analysis
Patient demographics and clinical characteristics, treatment patterns, and clinical outcomes were analyzed descriptively. ALK testing patterns were summarized by year and for the overall analysis period.
Results
Patients
A total of 60,025 adult patients with stage IIIB or IV NSCLC were eligible for this study. Of these, the majority (69.1%) had tumors with nonsquamous cell histology, 86.6% had a history of smoking, and most had stage IV disease at initial diagnosis (61.8% vs. 20.5% at stage III, 5.2% at stage II, and 9.0% at stage I).
Tumors from 36,691 (61.1%) patients were tested at least once for ALK alterations during the analysis period, and tumors from 23,334 (38.9%) patients were not tested (Figure 1). About 30.9% (n = 4719) of patients with squamous histology and 73.1% (n = 30,347) of patients with nonsquamous histology were tested for ALK alterations (Table S1). Testing rates were similar regardless of smoking status.
Among patients who underwent ALK testing, the median age was 69.0 (interquartile range [IQR]: 61-76) years, 45.1% were female, 62.1% were White, 66.6% had stage IV disease, 84.2% had a history of smoking, 82.7% had nonsquamous histology, 12.9% had squamous histology, and histology was not specified in 4.4% of patients. Patients who were not tested for ALK had a median age of 70.0 (IQR: 63-77) years, 39.7% were female, 63.5% were White, 54.4% had stage IV disease, 90.4% had a history of smoking, 47.8% had nonsquamous histology, 45.3% had squamous histology, and histology was not specified in 6.9% of patients (Table 1).
Table 1Baseline Demographics and Clinical Characteristics by ALK Status (N = 60,025)
Of patients who were tested, 1042 (2.8%) were positive and 35,649 (97.2%) were negative for ALK rearrangements. Among patients with an ALK+ test result, the median age was 63.0 (IQR: 54-72) years, 50.2% were female, 60.4% were White, 71.8% had stage IV disease, 46.7% had a history of smoking. 92.5% had nonsquamous histology, 3.6% had squamous histology, and histology was not specified in 3.8% of patients. Among patients with a negative ALK test result, the median age was 69.0 (IQR: 61-76) years, 45.0% were female, 62.2% were White, 66.4% had stage IV disease, 85.3% had a history of smoking, 82.4% had nonsquamous histology, 13.1% had squamous histology, and histology was not specified in 4.4% of patients (Table 1).
ALK Testing Patterns
The median time from diagnosis of advanced NSCLC to the date of the first ALK+ test result was 23 (IQR: 13-43) days (Table 2). The latency between diagnosis and the first ALK+ test result was similar between 2016 and 2019 (median: 25 days; IQR: 14-45) and for the entire study period (Table S2).
Table 2Time From Advanced Diagnosis Date to First ALK Test Date and Laboratory Processing Time
Over the duration of the analysis period, the rate of ALK testing increased from 33.1% in 2011 to 73.0% in 2019. Testing was lower for patients with squamous compared to nonsquamous histology. ALK testing rates increased over time for patients with nonsquamous (41.6%-81.6%) and squamous histology (13.6%-50.4%). Testing rates increased more rapidly among patients with squamous histology, with the largest increase occurring from 2016 to 2018 (31.2%-50.8%) (Figure 2).
Figure 2ALK testing rates and ALK TKI FDA approvals, by year of advanced diagnosis. Abbreviations: 1L = first-line; ALK = anaplastic lymphoma kinase; ALK = anaplastic lymphoma kinase gene; FDA = Food and Drug Administration; TKI = tyrosine kinase inhibitor.
The proportion of tests performed using FISH declined from 83.8% in 2012 to 32.1% in 2019. Conversely, the proportion of tests performed using NGS increased from 0.2% in 2011 to 52.2% in 2019 (Figure 3A). These patterns of ALK sequencing technology usage were reflected among patients with an ALK+ test result (Figure 3B). The proportion of tests that were positive for ALK alterations differed by sequencing technology, with 0.9% of PCR, 2.1% of NGS, and 3.0% of FISH tests reporting ALK+ results (Table S3).
Figure 3ALK sequencing technology usage, by year of test result for (A) all patients, and (B) all patients with an ALK+ test result a“Other” included testing types that represented a small proportion of tests, including proteomics, mass spectrometry, and FISH. b“Other sequencing” defined as sequencing methods other than NGS, including RNA sequencing, whole transcriptome shotgun sequencing, Sanger sequencing, direct sequencing, or if a sequencing test was performed just to test one gene, as opposed to a large panel of genes. Abbreviations: ALK = anaplastic lymphoma kinase gene; FISH = fluorescence in situ hybridization; IHC = immunohistochemistry; NGS = next-generation sequencing; PCR = polymerase chain reaction; RNA = ribonucleic acid.
Over the duration of the analysis period, sample types used for ALK testing were distributed as 85.1% solid tissue (biopsy) samples and 13.5% blood (liquid biopsy) (Table S4). The proportion of ALK tests performed using blood samples increased from 0.1% in 2011 to 28.2% in 2019, with the largest increase occurring from 2015 to 2019 (5.2%-28.2%). An opposing trend was observed with the use of tissue samples, which decreased from 98.0% in 2011 to 71.2% in 2019 (Figure 4). Patients may have had more than one test and the frequency of blood sample testing increased with repeat ALK testing, as only 9.1% of tests used to obtain a first ALK test result were performed on blood samples, compared to 28.4 and 38.6% of tests used to obtain second and third ALK test results, respectively (Table S4).
Figure 4Sample types used for ALK testing, by year of test result. Abbreviation: ALK = anaplastic lymphoma kinase gene.
The latency between the diagnosis of advanced NSCLC and the first ALK+ test result differed by sample type. Specifically, the first ALK+ test result was obtained at a median 22 (IQR: 13-40.5) days after diagnosis when tissue samples were used, compared to 30.5 (IQR: 17-69) days when blood samples were used. Although laboratory processing time was similar for both sample types, time from diagnosis to blood test date, and consequently test result, was longer (Table 2).
As shown in Figure 5, over the duration of the analysis period, relative frequencies of testing methods were unique to the sample type used, whereby most testing on tissue samples was performed using FISH (71.1%) followed by NGS (20.9%). When blood samples were tested, the most common testing methods were NGS (69.3%) followed by PCR (23.7%).
Figure 5Frequency of ALK testing by sequencing technology, by sample type during the analysis period. Abbreviations: ALK = anaplastic lymphoma kinase gene; FISH = fluorescence in situ hybridization; NGS = next-generation sequencing; PCR = polymerase chain reaction.
Treatment Patterns Before and After ALK Test Results
Among patients with at least one ALK+ test result (n = 983), 243 (24.7%) had initiated therapy prior to receiving their first ALK+ test result (Table 3). Most of these patients received their ALK+ test result prior to first-line therapy (Figure 6A). From 2011 to 2016, chemotherapy was the most common treatment for patients with ALK+ NSCLC who had not yet received their ALK+ test result, and in 2017 chemotherapy and IO agents were used at the same frequency in this patient population. From 2018 to 2019, IO agents were the most commonly initiated treatment for patients with ALK+ NSCLC who had not yet received the ALK test result (Figure 6B). Of the 983 patients with an ALK+ test result, 742 (75.5%) received an ALK TKI after their ALK+ test result. Among the 243 patients who initiated treatment prior to their ALK+ test result, 194 (79.8%) received an ALK TKI, including 123/144 (85.4%) patients who had originally initiated chemotherapy. Among patients who received an ALK TKI, treatment latency (median number of days from ALK+ test result to initiation of ALK TKI) was 22 days (IQR: 10-55). Among patients who initiated treatment prior to ALK test result, treatment latency was 32.5 days (IQR: 15-93) (Table 3). Details of the line of therapy when first ALK TKI was received are presented in Tables S5 and S6.
Figure 6Treatment characteristics of patients with ALK+ test result. (A) Line of therapy patients were receiving when the ALK+ test result was obtained, and (B) frequencies, by year of test result, of treatment types initiated by patients who were ALK+ but had yet to receive the ALK test result *28 patients who received ALK+ test result and initiated first-line treatment on the same day were considered “During first-line.” Abbreviations: ALK = anaplastic lymphoma kinase; ALK = anaplastic lymphoma kinase gene; chemo = chemotherapy; EGFR = epidermal growth factor receptor; IO = immuno-oncology; TKI = tyrosine kinase inhibitor.
An analysis of PD-L1 testing patterns in patients with advanced NSCLC revealed that between 75.4% and 77% of these patients had been tested for PD-L1 expression each year since 2017 (Figure S1). Median time from advanced diagnosis date to first PD-L1 test was 12 (IQR: 3-38.5) days, and time to first positive PD-L1 test was 20.5 (IQR: 10-36.5) days (Table S7). Among patients with a first ALK+ test result (n = 983), 158 (16.1%) received their first positive PD-L1 test result (defined as “PD-L1 positive” in patient chart review or PD-L1 tumor proportion score [TPS] > 1%) before their ALK+ test result. Of the 243 patients who initiated any treatment before receiving their first ALK+ test result, 41 (16.9%) had tested positive for PD-L1 prior to receiving the ALK+ test result. Of the 57 patients who initiated IO therapy prior to receiving their first ALK+ test result, 42 (73.7%) had received their first PD-L1 result, of whom 27 (47.4%) had received a positive PD-L1 test prior to obtaining their ALK+ test result (Table S8).
Discussion
This study assessed real-world ALK testing patterns and treatment in 60,025 patients with advanced NSCLC, a similar number of patients compared with other reports of advanced NSCLC in the Flatiron database.
Findings showed that ALK testing rates in patients with advanced NSCLC steadily increased over time from 33% in 2011 to 73% in 2019, but universal testing was not reached. Considering histological subtype by year of diagnosis, ALK testing rates in patients with squamous histology increased from 13.6% in 2011 to 50.4% in 2019. ALK testing rates in patients with nonsquamous histology increased from 41.6% in 2011 to 81.6% in 2019. As the current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) only recommend biomarker testing in select patients with nonsquamous histology,
Adherence to National Comprehensive Cancer Network ALK testing guidelines for patients with advanced non-small cell lung cancer in U.S. Community Medical Centers.
Clinical impact of adherence to NCCN guidelines for biomarker testing and first-line treatment in advanced non-small cell lung cancer (aNSCLC) using real-world electronic health record data.
Understanding factors associated with anaplastic lymphoma kinase testing delays in patients with non-small cell lung cancer in a large real-world oncology database.
These increases in ALK testing rates were likely influenced by several factors, including advances in testing methodologies that allow for more accurate detection of ALK rearrangements, recent development and approval of effective treatments targeting ALK rearrangements, and the addition of and/or updates to clinical treatment guidelines that have included biomarker testing recommendations since 2012.
Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.
Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.
current guidelines recommend biomarker testing at initial diagnosis in all metastatic nonsquamous cell disease, including NSCLC not otherwise specified (NOS).
Factors reported in the literature that are associated with a lower likelihood of ALK testing have been identified as histology (squamous or NSCLC diagnosed as NOS due to uncertain histological subtype compared to nonsquamous histology), a history of smoking (for nonsquamous histology), decreased Eastern Cooperative Oncology Group performance status at diagnosis, earlier stage disease at initial NSCLC diagnosis, advanced diagnosis prior to 2016, older age (≥50 years), male sex, noncommercial insurance, smaller practice size and volume, and non-Western US regions.
Adherence to National Comprehensive Cancer Network ALK testing guidelines for patients with advanced non-small cell lung cancer in U.S. Community Medical Centers.
Understanding factors associated with anaplastic lymphoma kinase testing delays in patients with non-small cell lung cancer in a large real-world oncology database.
the present analysis showed that NGS became the predominant ALK testing method in 2018, replacing FISH. This trend is likely to continue as numerous NGS methodologies allow detection of a significant number of actionable gene alterations; and current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for NSCLC recommend broad molecular profiling.
However, IHC and FISH may detect some ALK rearrangements not identified by NGS, with discrepancies commonly related to the highly complex genomic rearrangements found in the clinical specimens.
High performance of targeted next generation sequencing on variance detection in clinical tumor specimens in comparison with current conventional methods.
This study found that the turnaround time between diagnosis of advanced NSCLC and ALK+ test result was 3 to 4 weeks, exceeding the 2 weeks (10 working days) recommended by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.
Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology.
The delay in obtaining biomarker testing results may have been a factor leading to treatment initiation before confirmation of an ALK test result in approximately 25% of patients with an ALK+ test result in the present study. Evidence to support the need for timely ALK status confirmation was revealed in a recent chart review showing that patients who were diagnosed with advanced NSCLC and had biomarker results available at the initial oncology consultation could reach a treatment decision immediately (median of 0 days), compared to a significant delay of 22 days (P = .0008) when biomarker results were not yet available, which was in turn was associated with a delay in initiating treatment.
Biomarker testing of lung cancer specimens for gene rearrangement is important for the identification of potential efficacious targeted therapies and avoidance of therapies unlikely to provide clinical benefit or which cause unnecessary toxicity. Data from the present study showed that nearly one quarter of patients whose tumors would eventually be confirmed as ALK+ began treatment, most often chemotherapy, before receiving the result. A recent study demonstrated that initiation of chemotherapy before an ALK TKI in patients with ALK+ NSCLC was associated with a 30% increased risk of remaining untreated with an ALK TKI by 3 weeks after the ALK test result was received, and a 3-week delay in ALK TKI initiation more than doubled the risk of mortality.
In another real-world analysis, 94% of patients with ALK+ NSCLC who had been tested before initiating first-line therapy received targeted therapy compared to 65% of patients who had been tested after first-line therapy was underway.
In the 243 patients initiating treatment prior to ALK test results in the present study, 6 patients received an epidermal growth factor receptor (EGFR) TKI. Of these, all but 1 patient was diagnosed between 2011 and 2014 when ALK testing was less well recognized as a target biomarker. Although all 6 patients were tested for EGFR status, only 1 tested positive. It is unknown why these patients were initiated on an EGFR TKI despite the negative EGFR mutation testing result in 5 of 6 patients.
In the present study, beginning in 2016, the use of IO steadily increased to become the predominant first-line therapy by 2018 among patients who had not yet received their ALK+ test result. This likely reflected the prevailing standard of care with the approval of 3 IO agents.
Although evidence addressing IO therapy in patients in ALK+ NSCLC is limited, several analyses have demonstrated the relative lack of efficacy of IO monotherapy in these patients.
EGFR mutations and ALK rearrangements are associated with low response rates to PD-1 pathway blockade in non-small cell lung cancer: a retrospective analysis.
Severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, dermatologic reactions, and nephritis with renal dysfunction have been reported with IO use.
Phase 1/2 study of the safety and tolerability of nivolumab plus crizotinib for the first-line treatment of anaplastic lymphoma kinase translocation—positive advanced nonesmall cell lung cancer (CheckMate 370).
Felip E, De Braud FG, Maur M, et al. Ceritinib plus nivolumab (NIVO) in patients (pts) with anaplastic lymphoma kinase positive (ALKþ) advanced nonesmall cell lung cancer (NSCLC), Abstract Presented at: American Society of Clinical Oncology Annual Meeting June 2-6, 2017, Chicago, IL.
Among all patients with ALK+ NSCLC in the present study, 16.1% of patients received a positive PD-L1 test result before their ALK+ test result, whereas 47.4% of patients who initiated IO therapy prior to receiving their first ALK+ test result received a positive PD-L1 test result before their ALK+ test result. As PD-1/PD-L1 inhibitors are not recommended as first-line therapy in patients with ALK+ NSCLC, the finding that a substantial proportion of patients in this study initiated IO therapy prior to receiving ALK+ test results highlights the importance of performing biomarker testing immediately on diagnosis of advanced NSCLC, and the need for prioritization of therapies with the greatest potential for effectiveness in patients with ALK+ NSCLC.
Limitations
This study was limited by the retrospective design, the nature of observational data, and the retrospective investigation of medical records, for which quality control can vary. In this particular dataset, certain elements, such as dates of events, were frequently missing, and whether patients received multiple ALK tests and/or when such tests were performed were not always conclusive. Data granularity was limited for some variables, including detailed breakdown of PD-L1 levels, and specifics on type of NGS and FISH testing. As ALK rearrangements occur in both nonsmokers and smokers, it is essential to perform biomarker testing for all cases of NSCLC to guarantee complete identification of clinically relevant oncogenic drivers.
Conclusion
This real-world analysis revealed that testing for ALK rearrangements increased over time but had not reached 100% by the end of the study period (2019), despite treatment guideline recommendations. Further, 24.7% of patients with a first ALK+ test result initiated therapy prior to receiving the ALK+ test result. There is an unmet need for comprehensive and timely biomarker testing to ensure necessary molecular data is available for therapeutic planning and informed treatment decision making in patients with ALK+ NSCLC.
Clinical Practice Points
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Identification of ALK rearrangements in patients with advanced NSCLC helps select those patients who will derive benefit from ALK TKI therapy.
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Clinical practice guidelines recommend molecular profiling that includes ALK testing in patients with NSCLC.
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Real-world data from over 60,000 patients in the US showed the rate of ALK testing in advanced NSCLC increased from 33% to 73% between 2011 and 2019, indicating that more than a quarter of patients with NSCLC are not receiving recommended biomarker testing.
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Despite advancements in ALK testing technology, the median time between diagnosis of advanced NSCLC and obtaining an ALK-positive (ALK+) test result was 23 days.
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Due to delays between NSCLC diagnosis and receipt of ALK test results, nearly 25% of patients with ALK+ tumors initiated therapy prior to knowing ALK status.
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Delays in obtaining test results may have affected treatment decisions for some patients with ALK+ NSCLC; until 2018, prior to receiving an ALK+ test result, the most frequently initiated treatment was chemotherapy, followed by immuno-oncology therapy.
Acknowledgments
Medical writing support was provided by Jane Kondejewski, PhD of SNELL Medical Communication Inc., Montreal, Quebec, Canada, and funded by Takeda Development Center Americas, Inc, Lexington, MA, USA. This study was sponsored by Takeda Development Center Americas, Inc.
Disclosure
H.M.L., Y.W., Y.Y., H.N., E.A.C., and M.J.H. are employees of Takeda and may own stock. C.M.L. has served as a consultant to Amgen, Arrivent, Astra Zeneca, Blueprints Medicine, Cepheid, D2G Oncology, Daiichi Sankyo, Eli Lilly, EMD Serono, Foundation Medicine, Genentech, Illumina, Janssen, Medscape, Pfizer, Puma, Roche, Syros, and Takeda and has received research grants from AstraZeneca, Novartis, and Xcovery (none active now).
Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT).
Clinicopathological and demographical characteristics of non-small cell lung cancer patients with ALK rearrangements: a systematic review and meta-analysis.
First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study.
Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: guideline from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.
EGFR mutations and ALK rearrangements are associated with low response rates to PD-1 pathway blockade in non-small cell lung cancer: a retrospective analysis.
Birnbaum B, Nussbaum N, Seidl-Rathkopf K, et al. Model-assisted cohort selection with bias analysis for generating large-scale cohorts from the EHR for oncology research. 2020;arXiv:2001.09765v1.
Adherence to National Comprehensive Cancer Network ALK testing guidelines for patients with advanced non-small cell lung cancer in U.S. Community Medical Centers.
Clinical impact of adherence to NCCN guidelines for biomarker testing and first-line treatment in advanced non-small cell lung cancer (aNSCLC) using real-world electronic health record data.
Understanding factors associated with anaplastic lymphoma kinase testing delays in patients with non-small cell lung cancer in a large real-world oncology database.
High performance of targeted next generation sequencing on variance detection in clinical tumor specimens in comparison with current conventional methods.
Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology.
Phase 1/2 study of the safety and tolerability of nivolumab plus crizotinib for the first-line treatment of anaplastic lymphoma kinase translocation—positive advanced nonesmall cell lung cancer (CheckMate 370).
Felip E, De Braud FG, Maur M, et al. Ceritinib plus nivolumab (NIVO) in patients (pts) with anaplastic lymphoma kinase positive (ALKþ) advanced nonesmall cell lung cancer (NSCLC), Abstract Presented at: American Society of Clinical Oncology Annual Meeting June 2-6, 2017, Chicago, IL.
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