Advertisement

Real-world ALK Testing Trends in Patients With Advanced Non–Small-Cell Lung Cancer in the United States

Published:October 12, 2022DOI:https://doi.org/10.1016/j.cllc.2022.09.010

      Highlights

      • Tumors from 73% of patients with advanced NSCLC were tested for ALK rearrangements in 2019.
      • Approximately 3 weeks passed between NSCLC diagnosis and ALK test result.
      • In 2019, FISH and NGS were used for 32% and 52% of ALK tests, respectively.
      • 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.

      Keywords

      Abbreviations:

      ALK (anaplastic lymphoma kinase), ALK (anaplastic lymphoma kinase gene), Chemo (chemotherapy), EGFR (epidermal growth factor receptor), EHR (electronic health record), FDA (Food and Drug Administration), FISH (fluorescence in situ hybridization), IHC (immunohistochemistry), IO (immuno-oncology), IQR (interquartile range), NCCN (National Comprehensive Cancer Network (NCCN)), NGS (next-generation sequencing), NOS (not otherwise specified), NSCLC (non–small-cell lung cancer), PCR (polymerase chain reaction), Pd-1 (programmed cell death-1), Pd-L1 (programmed death-ligand 1), RNA (ribonucleic acid), TKI (tyrosine kinase inhibitor), TPS (tumor proportion score), UNK (unknown), US (United States)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Lung Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Barlesi F
        • Mazieres J
        • Merlio J-P
        • et al.
        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).
        Lancet. 2016; 387: 1415-1426https://doi.org/10.1016/S0140-6736(16)00004-0
        • Fan L
        • Feng Y
        • Wan H
        • Shi G
        • Niu W.
        Clinicopathological and demographical characteristics of non-small cell lung cancer patients with ALK rearrangements: a systematic review and meta-analysis.
        PLoS ONE. 2014; 9 (Addison CL, ed)e100866https://doi.org/10.1371/journal.pone.0100866
        • Gainor JF
        • Varghese AM
        • Ou S-HI
        • et al.
        ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non–small cell lung cancer.
        Clin Cancer Res. 2013; 19: 4273-4281https://doi.org/10.1158/1078-0432.CCR-13-0318
        • Peters S
        • Camidge DR
        • Shaw AT
        • et al.
        ALEX Trial Investigators. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer.
        N Engl J Med. 2017; 377 (Epub 2017 Jun 6. PMID: 28586279): 829-838https://doi.org/10.1056/NEJMoa1704795
        • Hida T
        • Nokihara H
        • Kondo M
        • et al.
        Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial.
        Lancet. 2017; 390 (Epub 2017 May 10): 29-39https://doi.org/10.1016/S0140-6736(17)30565-2
        • Camidge DR
        • Kim HR
        • Ahn MJ
        • et al.
        Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer.
        N Engl J Med. 2018; 379 (Epub 2018 Sep 25): 2027-2039https://doi.org/10.1056/NEJMoa1810171
        • Soria JC
        • Tan DSW
        • Chiari R
        • et al.
        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.
        Lancet. 2017; 389: 917-929https://doi.org/10.1016/S0140-6736(17)30123-X
        • Solomon BJ
        • Mok T
        • Kim DW
        • et al.
        PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer.
        N Engl J Med. 2014; 371: 2167-2177https://doi.org/10.1056/NEJMoa1408440
        • Shaw AT
        • Bauer TM
        • de Marinis F
        • et al.
        CROWN Trial Investigators. First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer.
        N Engl J Med. 2020; 383: 2018-2029https://doi.org/10.1056/NEJMoa2027187
        • Lindeman NI
        • Cagle PT
        • Aisner DL
        • et al.
        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.
        Arch Pathol Lab Med. 2018; 142: 321-346https://doi.org/10.5858/arpa.2017-0388-CP
      1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Guideline Name V.X.20XX. © National Comprehensive Cancer Network, Inc. 20XX. All rights reserved. Accessed [Month and Day, Year]. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

        • Lu YQ
        • Lu KH.
        Advancements in next-generation sequencing for diagnosis and treatment of non-small-cell lung cancer.
        Chronic Dis Transl Med. 2017; 3: 1-7https://doi.org/10.1016/j.cdtm.2017.02.009
        • Pai-Scherf L
        • Blumenthal GM
        • Li H
        • et al.
        FDA approval summary: pembrolizumab for treatment of metastatic non-small cell lung cancer: first-line therapy and beyond.
        Oncologist. 2017; 22 (Epub 2017 Aug 23): 1392-1399https://doi.org/10.1634/theoncologist.2017-0078
        • Kazandjian D
        • Suzman DL
        • Blumenthal G
        • et al.
        FDA approval summary: nivolumab for the treatment of metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapy.
        Oncologist. 2016; 21 (Epub 2016 Mar 16): 634-642https://doi.org/10.1634/theoncologist.2015-0507
        • Weinstock C
        • Khozin S
        • Suzman D
        • et al.
        U.S. Food and Drug Administration approval summary: atezolizumab for metastatic non-small cell lung cancer.
        Clin Cancer Res. 2017; 23 (Epub 2017 Jun 13. PMID: 28611199): 4534-4539https://doi.org/10.1158/1078-0432.CCR-17-0540
        • Jahanzeb M
        • Lin HM
        • Pan X
        • et al.
        Immunotherapy treatment patterns and outcomes among ALK-with non–small-cell lung cancer.
        Clin Lung Cancer. 2021; 22: 49-57https://doi.org/10.1016/j.cllc.2020.08.003
        • Mazieres J
        • Drilon A
        • Lusque A
        • et al.
        Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry.
        Ann Oncol. 2019; 30: 1321-1328https://doi.org/10.1093/annonc/mdz167
        • Gainor JF
        • Shaw AT
        • Sequist LV
        • et al.
        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.
        Clin Cancer Res. 2016; 22: 4585-4593https://doi.org/10.1158/1078-0432.CCR-15-3101
        • Calles A
        • Riess JW
        • Brahmer JR.
        Checkpoint blockade in lung cancer with driver mutation: choose the road wisely.
        Am Soc Clin Oncol Educ Book. 2020; 40: 372-384https://doi.org/10.1200/EDBK_280795
        • Ma X
        • Long L
        • Moon S
        • Adamson BJS
        • Baxi SS.
        Comparison of population characteristics in real-world clinical oncology databases in the US: Flatiron Health, SEER, and NPCR.
        medRxiv. 2020; (03.16.20037143)https://doi.org/10.1101/2020.03.16.20037143
      2. 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.

        • Liu R
        • Rizzo S
        • Whipple S
        • et al.
        Evaluating eligibility criteria of oncology trials using real-world data and AI.
        Nature. 2021; 592: 629-633
        • Illei PB
        • Wong W
        • Wu N
        • et al.
        ALK testing trends and patterns among community practices in the United States.
        JCO Precis Oncol. 2018; 2: 1-11https://doi.org/10.1200/PO.18.00159
        • Bernicker EH
        • Xiao Y
        • Abraham A
        • et al.
        Adherence to National Comprehensive Cancer Network ALK testing guidelines for patients with advanced non-small cell lung cancer in U.S. Community Medical Centers.
        Oncologist. 2021; 26: e1050-e1057https://doi.org/10.1002/onco.13779
        • Guérin A
        • Sasane M
        • Zhang J
        • et al.
        ALK rearrangement testing and treatment patterns for patients with ALK-positive non-small cell lung cancer.
        Cancer Epidemiol. 2015; 39 (Epub 2015 Apr 23): 307-312https://doi.org/10.1016/j.canep.2015.04.005
        • Waterhouse DM
        • Tseng WY
        • Espirito JL
        • Robert NJ.
        Understanding contemporary molecular biomarker testing rates and trends for metastatic NSCLC among community oncologists.
        Clin Lung Cancer. 2021; 22 (Epub 2021 May 29): e901-e910https://doi.org/10.1016/j.cllc.2021.05.006
        • John A
        • Yang B
        • Shah R.
        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.
        Adv Ther. 2021; 38 (Epub 2021 Feb 4): 1552-1566https://doi.org/10.1007/s12325-020-01617-2
        • Bernicker EH
        • Xiao Y
        • Croix DA
        • et al.
        Understanding factors associated with anaplastic lymphoma kinase testing delays in patients with non-small cell lung cancer in a large real-world oncology database.
        Arch Pathol Lab Med. 2022; 146: 975-983https://doi.org/10.5858/arpa.2021-0029-OA
        • Nadler E
        • Pavilack M
        • Clark J
        • Espirito J
        • Fernandes A
        Biomarker testing rates in patients with advanced non-small cell lung cancer treated in the community.
        J Cancer Ther. 2019; 10: 971-984https://doi.org/10.4236/jct.2019.1012083
        • Mino-Kenudson M.
        Immunohistochemistry for predictive biomarkers in non-small cell lung cancer.
        Transl Lung Cancer Res. 2017; 6: 570-587https://doi.org/10.21037/tlcr.2017.07.06
        • Teixidó C
        • Karachaliou N
        • Peg V
        • Gimenez-Capitan A
        • Rosell R.
        Concordance of IHC, FISH and RT-PCR for EML4-ALK rearrangements.
        Transl Lung Cancer Res. 2014; 3: 70-74https://doi.org/10.3978/j.issn.2218-6751.2014.02.02
        • Su D
        • Zhang D
        • Chen K
        • et al.
        High performance of targeted next generation sequencing on variance detection in clinical tumor specimens in comparison with current conventional methods.
        J Exp Clin Cancer Res. 2017; 36: 121https://doi.org/10.1186/s13046-017-0591-4
        • Lindeman NI
        • Cagle PT
        • Beasley MB
        • et al.
        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.
        J Thorac Oncol. 2013; 8: 823-859https://doi.org/10.1097/JTO.0b013e318290868f
        • Lim C
        • Tsao MS
        • Le LW
        • et al.
        Biomarker testing and time to treatment decision in patients with advanced nonsmall-cell lung cancer.
        Ann Oncol. 2015; 26: 1415-1421https://doi.org/10.1093/annonc/mdv208
        • Sheinson D
        • Wong WB
        • Wu N
        • Mansfield AS.
        Impact of delaying initiation of anaplastic lymphoma kinase inhibitor treatment on survival in patients with advanced non-small-cell lung cancer.
        Lung Cancer. 2020; 143: 86-92https://doi.org/10.1016/j.lungcan.2020.03.005
        • Ruggiero JE
        • Rughani J
        • Neiman J
        • et al.
        Real-world concordance of clinical practice with ASCO and NCCN guidelines for EGFR/ALK testing in aNSCLC.
        J Clin Oncol. 2017; 35 (212-212)https://doi.org/10.1200/JCO.2017.35.8_suppl.212
      3. OPDIVO (nivolumab) Injection [prescribing information]: Princeton, NJ: Bristol-Myers Squibb; 2022. Accessed July 30, 2022.

      4. TECENTRIQ (atezolizumab) Injection [prescribing information]: San Francisco, CA: Genentech Inc; 2022. Accessed July 30, 2022.

        • Lin JJ
        • Chin E
        • Yeap BY
        • et al.
        Increased hepatotoxicity associated with sequential immune checkpoint inhibitor and crizotinib therapy in patients with non-small cell lung cancer.
        J Thorac Oncol. 2019; 14: 135-140
        • Spigel DR
        • Reynolds C
        • Waterhouse D
        • et al.
        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).
        J Thorac Oncol. 2018; 13: 682-688
      5. 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.

        • Kim D-W
        • Gadgeel SM
        • Gettinger SN
        • et al.
        Safety and clinical activity results from a phase Ib study of alectinib plus atezolizumab in ALK+ advanced NSCLC (aNSCLC).
        J Clin Oncol. 2018; 36 (suppl; abstr 9009): 15s
        • Ribas A
        • Hu-Lieskovan S.
        What does PD-L1 positive or negative mean?.
        J Exp Med. 2016; 213: 2835-2840https://doi.org/10.1084/jem.20161462