First-Line Systemic Treatments for Stage IV Non-Small Cell Lung Cancer in California: Patterns of Care and Outcomes in a Real-World Setting

Abstract Background Multiple systemic treatments have been developed for stage IV non-small cell lung cancer (NSCLC), but their use and effect on outcomes at the population level are unknown. This study describes the utilization of first-line systemic treatments among stage IV NSCLC patients in California and compares survival among treatment groups. Methods Data on 17 254 patients diagnosed with stage IV NSCLC from 2012 to 2014 were obtained from the California Cancer Registry. Systemic treatments were classified into six groups. The Kaplan-Meier method and multivariable Cox proportional hazards models were used to compare survival between treatment groups. Results Fifty-one percent of patients were known to have received systemic treatment. For patients with nonsquamous histology, pemetrexed regimens were the most common treatment (14.8%) followed by tyrosine kinase inhibitors (11.9%) and platinum doublets (11.5%). Few patients received pemetrexed/bevacizumab combinations (4.5%), bevacizumab combinations (3.6%), or single agents (1.7%). There was statistically significantly better overall survival for those on pemetrexed regimens (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.80 to 0.92), bevacizumab regimens (HR = 0.73, 95% CI = 0.65 to 0.81), pemetrexed/bevacizumab regimens (HR = 0.68, 95% CI = 0.61 to 0.76), or tyrosine kinase inhibitors (HR = 0.62, 95% CI = 0.57 to 0.67) compared with platinum doublets. The odds of receiving most systemic treatments decreased with decreasing socioeconomic status. For patients with squamous histology, platinum doublets were predominant (33.7%) and were not found to have statistically significantly different overall survival from single agents. Conclusions These population-level findings indicate low utilization of systemic treatments, survival differences between treatment groups, and evident treatment disparities by socioeconomic status.

[1]  H. Howe.  North American Association of Central Cancer Registries , 2020, Definitions.

[2]  C. Fuller,et al.  Barriers to Combined-Modality Therapy for Limited-Stage Small Cell Lung Cancer , 2018, JAMA oncology.

[3]  L. Muffly,et al.  Decreased early mortality associated with the treatment of acute myeloid leukemia at National Cancer Institute‐designated cancer centers in California , 2018, Cancer.

[4]  M. Reck,et al.  Pembrolizumab as first-line therapy for metastatic non-small-cell lung cancer. , 2018, Immunotherapy.

[5]  J. McCubrey,et al.  Bevacizumab in the treatment of NSCLC: patient selection and perspectives , 2017, Lung Cancer.

[6]  K. Kizer,et al.  Disparities in quality of cancer care , 2017, Medicine.

[7]  U. Ladabaum,et al.  Trends in Cancer Survival by Health Insurance Status in California From 1997 to 2014 , 2017, JAMA oncology.

[8]  K. Kizer,et al.  Comorbidity index in central cancer registries: the value of hospital discharge data , 2017, Clinical epidemiology.

[9]  K. Mori,et al.  Real-world practice patterns for patients with advanced non-small cell lung cancer: multicenter retrospective cohort study in Japan , 2017, Lung Cancer.

[10]  P. Tassone,et al.  Radiotherapy prolongs the survival of advanced non-small-cell lung cancer patients undergone to an immune-modulating treatment with dose-fractioned cisplatin and metronomic etoposide and bevacizumab (mPEBev) , 2017, Oncotarget.

[11]  D. Ettinger,et al.  The next frontier in non-small cell lung cancer: synergizing radiation therapy and immune checkpoint blockade. , 2017, Clinical advances in hematology & oncology : H&O.

[12]  Yi-long Wu,et al.  A multicenter survey of first-line treatment patterns and gene aberration test status of patients with unresectable Stage IIIB/IV nonsquamous non-small cell lung cancer in China (CTONG 1506) , 2017, BMC Cancer.

[13]  A. Abernethy,et al.  Real-world first-line treatment and overall survival in non-small cell lung cancer without known EGFR mutations or ALK rearrangements in US community oncology setting , 2017, PloS one.

[14]  N. Blais,et al.  Factors influencing treatment selection and survival in advanced lung cancer. , 2017, Current oncology.

[15]  K. Kelly,et al.  Increasing Rates of No Treatment in Advanced‐Stage Non–Small Cell Lung Cancer Patients: A Propensity‐Matched Analysis , 2017, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[16]  B. Monk,et al.  Barriers to the Access of Bevacizumab in Patients with Solid Tumors and the Potential Impact of Biosimilars: A Physician Survey , 2017, Pharmaceuticals.

[17]  N. Rashid,et al.  Treatment Patterns and Overall Survival Associated with First-Line Systemic Therapy for Patients with Advanced Non-Small Cell Lung Cancer. , 2017, Journal of managed care & specialty pharmacy.

[18]  F. Hirsch,et al.  New and emerging targeted treatments in advanced non-small-cell lung cancer , 2016, The Lancet.

[19]  G. Nicholas,et al.  Palliative systemic therapy for advanced non-small cell lung cancer: Investigating disparities between patients who are treated versus those who are not. , 2016, Lung cancer.

[20]  L. Enewold,et al.  Real-World Patterns of EGFR Testing and Treatment with Erlotinib for Non-Small Cell Lung Cancer in the United States , 2016, PloS one.

[21]  K. Dwan,et al.  First-line treatment of advanced epidermal growth factor receptor ( EGFR ) mutation positive non-squamous non-small cell lung cancer Review information Review type : Intervention , 2015 .

[22]  R. Cress,et al.  Underutilization of gene expression profiling for early-stage breast cancer in California , 2016, Cancer Causes & Control.

[23]  A. Rossi,et al.  Platinum-based chemotherapy in advanced non-small-cell lung cancer: optimal number of treatment cycles , 2016, Expert review of anticancer therapy.

[24]  R. Perez-soler,et al.  Medical Treatment in Elderly Patients with Non-Small Cell Lung Cancer , 2016, Current Treatment Options in Oncology.

[25]  A. Harugeri,et al.  Elderly patients’ participation in clinical trials , 2015, Perspectives in clinical research.

[26]  K. Kizer,et al.  Disparities in Stage at Diagnosis, Survival, and Quality of Cancer Care in California by Source of Health Insurance , 2015 .

[27]  J. Austin,et al.  The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. , 2015, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[28]  R. McCormack,et al.  EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). , 2015, American journal of cancer research.

[29]  Craig C Earle,et al.  Real‐world chemotherapy treatment patterns in metastatic non–small cell lung cancer: Are patients undertreated? , 2015, Cancer.

[30]  A. Ziogas,et al.  Impact of National Cancer Institute Comprehensive Cancer Centers on ovarian cancer treatment and survival. , 2015, Journal of the American College of Surgeons.

[31]  J. Soria,et al.  Bevacizumab in Patients with Nonsquamous Non–Small Cell Lung Cancer and Asymptomatic, Untreated Brain Metastases (BRAIN): A Nonrandomized, Phase II Study , 2015, Clinical Cancer Research.

[32]  C. Drake,et al.  Stereotactic Radiation Therapy Augments Antigen-Specific PD-1–Mediated Antitumor Immune Responses via Cross-Presentation of Tumor Antigen , 2014, Cancer Immunology Research.

[33]  F. Cappuzzo,et al.  First-line crizotinib versus chemotherapy in ALK-positive lung cancer. , 2014, The New England journal of medicine.

[34]  Jeffrey W. Clark,et al.  Crizotinib in ROS1-rearranged non-small-cell lung cancer. , 2014, The New England journal of medicine.

[35]  A. Mahipal,et al.  Participation of the elderly population in clinical trials: barriers and solutions. , 2014, Cancer control : journal of the Moffitt Cancer Center.

[36]  Ming-Hui Chen,et al.  Cancer-specific outcomes among young adults without health insurance. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[37]  S. Thongprasert,et al.  A Prospective, Molecular Epidemiology Study of EGFR Mutations in Asian Patients with Advanced Non–Small-Cell Lung Cancer of Adenocarcinoma Histology (PIONEER) , 2014, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[38]  R. Dudley,et al.  Do Hospitals that Serve a High Percentage of Medicaid Patients Perform Well on Evidence-based Guidelines for Colon Cancer Care? , 2013, Journal of health care for the poor and underserved.

[39]  G. Giaccone,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. , 2013, The Journal of molecular diagnostics : JMD.

[40]  Michael Thomas,et al.  Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. , 2013, The New England journal of medicine.

[41]  G. Sonpavde,et al.  Prevalence and characteristics of patients with metastatic cancer who receive no anticancer therapy , 2012, Cancer.

[42]  N. Buckley,et al.  The role of comorbidities on the uptake of systemic treatment and 3-year survival in older cancer patients. , 2012 .

[43]  L. Holmberg,et al.  Social differences in lung cancer management and survival in South East England: a cohort study , 2012, BMJ Open.

[44]  F. Shepherd,et al.  Adjuvant chemotherapy for non-small-cell lung cancer in the elderly: a population-based study in Ontario, Canada. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  Jun Ma,et al.  Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. , 2011, The Lancet. Oncology.

[46]  G. Giaccone,et al.  American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) Mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[47]  A. Gemma,et al.  F1000 highlights , 2010 .

[48]  T. Younis,et al.  Adjuvant Chemotherapy Uptake in Non-small Cell Lung Cancer , 2008, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[49]  Johan Vansteenkiste,et al.  Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[50]  J. Fulton,et al.  Treatment Variation by Insurance Status for Breast Cancer Patients , 2008, The breast journal.

[51]  Robert Gray,et al.  Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. , 2006, The New England journal of medicine.

[52]  F. Shepherd,et al.  Platinum-based versus non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a meta-analysis of the published literature. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[53]  J. Gardiner,et al.  Cancer, Medicaid enrollment, and survival disparities , 2005, Cancer.

[54]  R. Deyo,et al.  Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. , 1992, Journal of clinical epidemiology.

[55]  G. Silversmit,et al.  Patterns of care for non‐small cell lung cancer patients in Belgium: A population‐based study , 2018, European journal of cancer care.

[56]  D. Brizel,et al.  National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology , 2012 .

[57]  E. Feuer,et al.  SEER Cancer Statistics Review, 1975-2003 , 2006 .