Next-Generation Sequencing Trends among Adult Patients with Select Advanced Tumor Types

Abstract

There are limited data on the prevalence of next-generation sequencing (NGS) in the United States, especially in light of the increasing importance of identifying actionable oncogenic variants due to molecular biomarker-based therapy approvals. This retrospective study of adult patients with select metastatic solid tumors and central nervous system tumors from the Optum Clinformatics Data Mart US health care claims database (January 1, 2014, to June 30, 2021; N = 63,209) examined NGS use trends over time. A modest increase in NGS was observed across tumor types from 2015 (0.0% to 1.5%) to 2021 (2.1% to 17.4%). A similar increase in NGS rates was also observed across key periods; however, rates in the final key period remained <10% for patients with breast, colorectal, head and neck, soft tissue sarcoma, and thyroid cancers, as well as central nervous system tumors. The median time to NGS from diagnosis was shortest among patients with non–small-cell lung cancer and longest for patients with breast cancer. Predictors of NGS varied by tumor type; test rates for minorities in select tumor types appeared comparable to the White population. Despite improving payer policies to expand coverage of NGS and molecular biomarker-based therapy approvals, NGS rates remained low across tumor types. Given the potential for improved patient outcomes with molecular biomarker-based therapy, further efforts to improve NGS rates are warranted. There are limited data on the prevalence of next-generation sequencing (NGS) in the United States, especially in light of the increasing importance of identifying actionable oncogenic variants due to molecular biomarker-based therapy approvals. This retrospective study of adult patients with select metastatic solid tumors and central nervous system tumors from the Optum Clinformatics Data Mart US health care claims database (January 1, 2014, to June 30, 2021; N = 63,209) examined NGS use trends over time. A modest increase in NGS was observed across tumor types from 2015 (0.0% to 1.5%) to 2021 (2.1% to 17.4%). A similar increase in NGS rates was also observed across key periods; however, rates in the final key period remained <10% for patients with breast, colorectal, head and neck, soft tissue sarcoma, and thyroid cancers, as well as central nervous system tumors. The median time to NGS from diagnosis was shortest among patients with non–small-cell lung cancer and longest for patients with breast cancer. Predictors of NGS varied by tumor type; test rates for minorities in select tumor types appeared comparable to the White population. Despite improving payer policies to expand coverage of NGS and molecular biomarker-based therapy approvals, NGS rates remained low across tumor types. Given the potential for improved patient outcomes with molecular biomarker-based therapy, further efforts to improve NGS rates are warranted. •Next-generation sequencing (NGS) is an increasingly important component of cancer care to enable identification of actionable genomic variants; however, there are limited data on the current prevalence of NGS in the United States, especially in light of the increasing importance of identifying actionable oncogenic variants due to molecular biomarker-based therapy approvals.•This study demonstrated an increase in NGS across a variety of tumor types from 2015 (0.0% to 1.5%) to 2021 (2.1% to 17.4%); metastatic non–small-cell lung cancer and metastatic breast cancer had the highest and lowest NGS rates in 2021, respectively. One potential reason for the differences in NGS rates between tumor types may be the variation seen in guideline recommendations for NGS.•NGS rates in the final key time period evaluated in this study (post-larotrectinib approval; November 26, 2018, to June 30, 2021) remained <10% for patients with metastatic breast cancer, central nervous system tumors, metastatic colorectal cancer, metastatic head and neck cancer, metastatic soft tissue sarcoma, and radioactive iodine-refractory metastatic thyroid carcinoma.•Despite improved coverage determinations and tumor-agnostic therapeutic approvals, NGS rates remained low overall in this study, and further efforts to improve NGS rates are indicated, especially given the potential for improved patient outcomes with molecular biomarker-based therapy. Precision cancer medicine is based on discovering specific targetable genomic variants.1Freedman A.N. Klabunde C.N. Wiant K. Enewold L. Gray S.W. Filipski K.K. Keating N.L. Leonard D.G.B. Lively T. McNeel T.S. Minasian L. Potosky A.L. Rivera D.R. Schilsky R.L. Schrag D. Simonds N.I. Sineshaw H.M. Struewing J.P. Willis G. de Moor J.S. Use of next-generation sequencing tests to guide cancer treatment: results from a nationally representative survey of oncologists in the United States.JCO Precis Oncol. 2018; 2PO.18.00169Google Scholar, 2Yates L.R. Seoane J. Le Tourneau C. Siu L.L. Marais R. Michiels S. Soria J.C. Campbell P. Normanno N. Scarpa A. Reis-Filho J.S. Rodon J. Swanton C. Andre F. The European Society for Medical Oncology (ESMO) precision medicine glossary.Ann Oncol. 2018; 29: 30-35Google Scholar, 3Gagan J. Van Allen E.M. Next-generation sequencing to guide cancer therapy.Genome Med. 2015; 7: 80Google Scholar Although historically cancer treatment followed a one-size-fits-all approach of categorizing cancers by histology alone, targetable genomic variants resulted in a shift in oncology practice with a focus on specific oncogenic variants.1Freedman A.N. Klabunde C.N. Wiant K. Enewold L. Gray S.W. Filipski K.K. Keating N.L. Leonard D.G.B. Lively T. McNeel T.S. Minasian L. Potosky A.L. Rivera D.R. Schilsky R.L. Schrag D. Simonds N.I. Sineshaw H.M. Struewing J.P. Willis G. de Moor J.S. Use of next-generation sequencing tests to guide cancer treatment: results from a nationally representative survey of oncologists in the United States.JCO Precis Oncol. 2018; 2PO.18.00169Google Scholar, 2Yates L.R. Seoane J. Le Tourneau C. Siu L.L. Marais R. Michiels S. Soria J.C. Campbell P. Normanno N. Scarpa A. Reis-Filho J.S. Rodon J. Swanton C. Andre F. The European Society for Medical Oncology (ESMO) precision medicine glossary.Ann Oncol. 2018; 29: 30-35Google Scholar, 3Gagan J. Van Allen E.M. Next-generation sequencing to guide cancer therapy.Genome Med. 2015; 7: 80Google Scholar Numerous genomic variants have been reported across a wide range of solid tumor histologies, many of which are observed with an overall low frequency but may serve as the primary oncogenic variant of the tumor.4Westphalen C.B. Krebs M.G. Le Tourneau C. Sokol E.S. Maund S.L. Wilson T.R. Jin D.X. Newberg J.Y. Fabrizio D. Veronese L. Thomas M. de Braud F. Genomic context of NTRK1/2/3 fusion-positive tumours from a large real-world population.NPJ Precis Oncol. 2021; 5: 69Google Scholar,5Stransky N. Cerami E. Schalm S. Kim J.L. Lengauer C. The landscape of kinase fusions in cancer.Nat Commun. 2014; 5: 4846Google Scholar There are currently numerous therapies that target oncogenic variants within specific tumor histologies [eg, ALK, ROS1, and EGFR in non–small-cell lung cancer (NSCLC)].6Malone E.R. Oliva M. Sabatini P.J.B. Siu L.L. for precision cancer Med. Scholar, N. guideline for the of lung cancer patients for treatment with kinase Society of Oncology of the of for the of for practice guideline 2018; Scholar, N.I. C. S. K. M. L. R. E. C.B. molecular guideline for the of lung cancer patients for treatment with kinase guideline from the of the for the of and the for 2018; Scholar there are tumor-agnostic therapies that are to target specific oncogenic variants and of tumor F. R. in the to the patient with the Scholar One of the US and tumor-agnostic therapies was which was in November The of molecular biomarker-based therapies to for patients with metastatic cancer in A. F. P. S. A. sequencing of lung based on and on 2021; Scholar, N. G. R. D.R. The of in treatment on Med. Scholar, A. M. of precision medicine in lung real-world outcomes with the use of Scholar, N. J. A the of sequencing to in patients with lung cancer in the United Oncol. Scholar, C. Michiels S. C. Le L. A. L. E. S. S. M. R. A. A. S. C. N. T. F. P. J.Y. C. E. E. G. A. Andre F. Soria J.C. and in results of the 7: Scholar, M. M. Schilsky R.L. J. R. of biomarker-based treatment with rates and in a Oncol. Scholar, M. C. Schilsky R.L. J. R. of a biomarker-based on oncology a of to 2015; Scholar, M. M. Schilsky R.L. J. R. of precision medicine in a of Oncol. 2015; Scholar, M. S. J. R. Precision the Scholar, A. S. S. F. C. R. P. R. Precision outcomes to the and treatment Oncol. 2018; Scholar, Van G. T. S. D. K. R. A retrospective of precision medicine outcomes in patients with cancer improved health care Scholar of the landscape of molecular biomarker-based therapies and molecular increasingly with the of tumor-agnostic therapies that target genomic variants that low across many solid tumors, is to have a to genomic variants to improve patient R. R. N. A. F. M. a sequencing test in a patient with Scholar numerous are to genomic which sequencing molecular and next-generation sequencing molecular in with and J. R. A. G. The of next-generation sequencing on Scholar of in and test for a a limited of genomic variants tests tests to to actionable genomic which may tissue and is in a in treatment A. A. T. A. M. of next-generation sequencing to genomic in metastatic lung cancer a Precis Oncol. Scholar with NGS low of NGS are a that for sequencing of genomic in a for of a variety of genomic variants and large and and with and S. S. D. R. S. R. Next-generation and in cancer Scholar NGS the identification of actionable genomic a low overall frequency across the and the of tissue C. S. between coverage and of next-generation 2021; Scholar a reported that NGS a to actionable genomic variants in cancer A. N. E. J. C. G. therapies in a genomic Scholar guideline recommendations also NGS in solid N. guideline for the of lung cancer patients for treatment with kinase Society of Oncology of the of for the of for practice guideline 2018; N.I. C. S. K. M. L. R. E. C.B. molecular guideline for the of lung cancer patients for treatment with kinase guideline from the of the for the of and the for 2018; D. A. J. N.I. K. S. J. Gray S.W. J. C. Andre F. N. M. L. M. F. genomic in patients with metastatic Oncol. Scholar, C. Willis J. J. C. R. C.B. for the of colorectal guideline from the Society for of for and Society of Scholar, N.L. A. K. P. R. E. M. A. for therapy in metastatic breast guideline Oncol. Scholar to that the Society of Oncology that for patient with metastatic solid tumors, genomic genomic sequencing as NGS with is patients are for a genomic therapy that a N. guideline for the of lung cancer patients for treatment with kinase Society of Oncology of the of for the of for practice guideline 2018; N.I. C. S. K. M. L. R. E. C.B. molecular guideline for the of lung cancer patients for treatment with kinase guideline from the of the for the of and the for 2018; D. A. J. N.I. K. S. J. Gray S.W. J. C. Andre F. N. M. L. M. F. genomic in patients with metastatic Oncol. Scholar, C. Willis J. J. C. R. C.B. for the of colorectal guideline from the Society for of for and Society of Scholar, N.L. A. K. P. R. E. M. A. for therapy in metastatic breast guideline Oncol. Scholar tumor-agnostic in the United States, and currently this Society of Oncology that patients with metastatic solid tumors have NGS in treatment F. R. in the to the patient with the D. A. J. N.I. K. S. J. Gray S.W. J. C. Andre F. N. M. L. M. F. genomic in patients with metastatic Oncol. Scholar Despite the of oncogenic variants and guideline recommendations with to in practice may of of and of NGS with of of and A.N. Klabunde C.N. Wiant K. Enewold L. Gray S.W. Filipski K.K. Keating N.L. Leonard D.G.B. Lively T. McNeel T.S. Minasian L. Potosky A.L. Rivera D.R. Schilsky R.L. Schrag D. Simonds N.I. Sineshaw H.M. Struewing J.P. Willis G. de Moor J.S. Use of next-generation sequencing tests to guide cancer treatment: results from a nationally representative survey of oncologists in the United States.JCO Precis Oncol. 2018; 2PO.18.00169Google R. P. T. Siu L.L. of tumor in an survey among Oncol. Scholar, R. N. J. A. G. to next-generation sequencing US survey Oncol. 2021; Scholar, R. J. N. J. L. S. R. M. and real-world outcomes of sequencing in patients with an study on the of based on Scholar of NGS by payer there been modest in the as coverage of The United for molecular oncology coverage in 30, and the for for NGS was in 30, of the landscape of molecular biomarker-based therapy with improved patient outcomes in solid tumors and the for molecular is to molecular A.N. Klabunde C.N. Wiant K. Enewold L. Gray S.W. Filipski K.K. Keating N.L. Leonard D.G.B. Lively T. McNeel T.S. Minasian L. Potosky A.L. Rivera D.R. Schilsky R.L. Schrag D. Simonds N.I. Sineshaw H.M. Struewing J.P. Willis G. de Moor J.S. Use of next-generation sequencing tests to guide cancer treatment: results from a nationally representative survey of oncologists in the United States.JCO Precis Oncol. 2018; 2PO.18.00169Google C. Michiels S. C. Le L. A. L. E. S. S. M. R. A. A. S. C. N. T. F. P. J.Y. C. E. E. G. A. Andre F. Soria J.C. and in results of the 7: Scholar, M. M. Schilsky R.L. J. R. of biomarker-based treatment with rates and in a Oncol. Scholar, M. C. Schilsky R.L. J. R. of a biomarker-based on oncology a of to 2015; Scholar, M. M. Schilsky R.L. J. R. of precision medicine in a of Oncol. 2015; Scholar, M. S. J. R. Precision the Scholar, A. S. S. F. C. R. P. R. Precision outcomes to the and treatment Oncol. 2018; Scholar, Van G. T. S. D. K. R. A retrospective of precision medicine outcomes in patients with cancer improved health care C. S. between coverage and of next-generation 2021; J. G. N. E. J. S. of molecular next-generation sequencing in the of patients with lung cancer in a F. Kim J. S. M. and treatment outcomes in patients with lung cancer and a from the Oncol. Scholar Although there are numerous to molecular in across solid tumors, there are limited data that the current prevalence of NGS in the United coverage of NGS and tumor-agnostic therapeutic C. S. between coverage and of next-generation 2021; Scholar NGS use over the health to patient may as NGS rates to have a for and patients with White S. C. in use of next-generation sequencing in patients with solid tumors by and of the coverage 2021; Scholar of trends in NGS use by patient and and across solid tumor may a of have to this study to the prevalence of NGS and patient and with NGS among adult patients with specific tumor types. A retrospective was the Optum Clinformatics Data Mart US health care claims database from 1, 2014, to June 30, The patient identification period was from 1, to US adult patients with select metastatic cancers soft tissue sarcoma, head and neck cancer radioactive thyroid colorectal cancer and breast as well as primary central nervous system tumors, cancers to solid tumors with therapies and guideline recommendations for molecular D. A. J. N.I. K. S. J. Gray S.W. J. C. Andre F. N. M. L. M. F. genomic in patients with metastatic Oncol. 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C. S. K. M. L. R. E. C.B. molecular guideline for the of lung cancer patients for treatment with kinase guideline from the of the for the of and the for 2018; D. A. J. N.I. K. S. J. Gray S.W. J. C. Andre F. N. M. L. M. F. genomic in patients with metastatic Oncol. Scholar, C. Willis J. J. C. R. C.B. for the of colorectal guideline from the Society for of for and Society of Scholar, N.L. A. K. P. R. E. M. A. for therapy in metastatic breast guideline Oncol. S. J. L. K. M. L. of genomic in treatment and improving patient outcomes in lung Med. 2021; Scholar A study by C. 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C.B. molecular guideline for the of lung cancer patients for treatment with kinase guideline from the of the for the of and the for 2018; Scholar also genomic variants with US and J. lung cancer and of Scholar health care may a in the variation in NGS across tumor types. for tumor types with targetable genomic variants guideline recommendations specific to there may be a of Although is important to NGS in patients with cancer, is also that NGS results are to results are for treatment limited data the time from diagnosis to NGS are A. E. E. T. R. A. C. A. D. L. L. NGS in lung cancer and metastatic breast cancer to Oncol. 2021; Scholar A. E. E. T. R. A. C. A. D. L. L. NGS in lung cancer and metastatic breast cancer to Oncol. 2021; Scholar evaluated time to NGS among patients with and Although study evaluated a from diagnosis to NGS time from diagnosis to NGS as was in the current the demonstrated that patients with had a time from diagnosis to NGS results patients with A. E. E. T. R. A. 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Scholar differences in NGS rates in patients with observed based on payer and of care have also that molecular in based on as and A. de F. S. A. T. A. de J. and treatment for patients with lung 2018; N. L. R. K. trends and among in the United States.JCO Precis Oncol. 2018; Scholar the current study, potential of NGS also varied by tumor and and and and payer and and and on the of and on NGS rates been A retrospective by S. C. in use of next-generation sequencing in patients with solid tumors by and of the coverage 2021; Scholar evaluated the of and on NGS among patients with from 1, = and and that Although NGS rates for and the for in 2018, results demonstrated that the increase in NGS use from the period to the period was = among patients and = among patients with White in A. F. P. S. A. sequencing of lung based on and on 2021; Scholar a large database of patients with NGS as of care between and = and to the potential differences in NGS this study, in NGS use based on was reported = to the from S. C. in use of next-generation sequencing in patients with solid tumors by and of the coverage 2021; Scholar from this which evaluated NGS rates within a similar payer also reported that NGS rates between 2015 and 2021 for and minorities in and primary tumors. from this differences by to with the results by A. F. P. S. A. sequencing of lung based on and on 2021; Scholar as NGS rates in and minorities in this study appeared comparable to the White population. that to health in a to to NGS between This study had this was health care claims data from a health and may the United as a of health care use of the health The database for this limited practice as practice may be a for and on to genomic is to this of the of patient identification have been by and the for molecular was for NGS rates may have been among patients study among the of patients for NGS was data have also to the of of of NGS in may be by of specific to NGS molecular as for in an patients in the and patient with an especially low of patients the to on trends in NGS in tumor types is Although this was a study and of a for was in this the study period for this the which may have health care improving payer coverage determinations and molecular biomarker-based and tumor-agnostic therapeutic approvals, NGS rates remained low overall in this solid tumor patient from the Optum Clinformatics Data Mart US health care claims in NGS rates observed across tumor types and across time with NGS as time NGS rates for minorities in and primary tumors across key time and appeared comparable to the White to health in a to to NGS of the data for NGS rates across solid tumors especially in light of the in and payer coverage further are to and for efforts to improve NGS rates that patients may therapeutic The use of genomic NGS the potential to molecular biomarker-based therapy on a with in health outcomes health care is to the to use of NGS and that to

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