Journal Article
. 2020 Apr;3(3).
doi: 10.1093/jncics/pkz020.

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

Frances B Maguire 1 Cyllene R Morris 1 Arti Parikh-Patel 1 Rosemary D Cress 2 Theresa H M Keegan 3 Chin-Shang Li 4 Patrick S Lin 3 Kenneth W Kizer 1 
  • PMID: 32328551
  •     52 References
  •     3 citations


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.

Real-World Patterns of EGFR Testing and Treatment with Erlotinib for Non-Small Cell Lung Cancer in the United States.
Lindsey Enewold, Anish Thomas.
PLoS One, 2016 Jun 15; 11(6). PMID: 27294665    Free PMC article.
Factors influencing treatment selection and survival in advanced lung cancer.
S Tabchi, E Kassouf, +2 authors, N Blais.
Curr Oncol, 2017 May 12; 24(2). PMID: 28490934    Free PMC article.
Impact of National Cancer Institute Comprehensive Cancer Centers on ovarian cancer treatment and survival.
Robert E Bristow, Jenny Chang, +3 authors, Hoda Anton-Culver.
J Am Coll Surg, 2015 Apr 05; 220(5). PMID: 25840536    Free PMC article.
Platinum-based versus non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a meta-analysis of the published literature.
Giannicola D'Addario, Melania Pintilie, +3 authors, Frances A Shepherd.
J Clin Oncol, 2005 Feb 25; 23(13). PMID: 15728229
New and emerging targeted treatments in advanced non-small-cell lung cancer.
Fred R Hirsch, Kenichi Suda, Jacinta Wiens, Paul A Bunn.
Lancet, 2016 Sep 07; 388(10048). PMID: 27598681
Highly Cited. Review.
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.
Caicun Zhou, Yi-Long Wu, +21 authors, Changxuan You.
Lancet Oncol, 2011 Jul 26; 12(8). PMID: 21783417
Highly Cited.
Underutilization of gene expression profiling for early-stage breast cancer in California.
Rosemary D Cress, Yingjia S Chen, +2 authors, Kenneth W Kizer.
Cancer Causes Control, 2016 Apr 22; 27(6). PMID: 27097910    Free PMC article.
Prevalence and characteristics of patients with metastatic cancer who receive no anticancer therapy.
Alexander C Small, Che-Kai Tsao, +7 authors, Matthew D Galsky.
Cancer, 2012 Jun 19; 118(23). PMID: 22707387
Comorbidity index in central cancer registries: the value of hospital discharge data.
Daphne Y Lichtensztajn, Brenda M Giddings, +2 authors, Kenneth W Kizer.
Clin Epidemiol, 2017 Dec 05; 9. PMID: 29200890    Free PMC article.
Medical Treatment in Elderly Patients with Non-Small Cell Lung Cancer.
Kamila Bakirhan, Janaki Sharma, Roman Perez-Soler, Haiying Cheng.
Curr Treat Options Oncol, 2016 Mar 05; 17(3). PMID: 26942588
Bevacizumab in the treatment of NSCLC: patient selection and perspectives.
Alessia E Russo, Domenico Priolo, +3 authors, Francesco Ferraù.
Lung Cancer (Auckl), 2017 Dec 26; 8. PMID: 29276417    Free PMC article.
The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification.
William D Travis, Elisabeth Brambilla, +17 authors, WHO Panel.
J Thorac Oncol, 2015 Aug 21; 10(9). PMID: 26291008
Highly Cited.
Barriers to the Access of Bevacizumab in Patients with Solid Tumors and the Potential Impact of Biosimilars: A Physician Survey.
Bradley J Monk, Philip E Lammers, Thomas Cartwright, Ira Jacobs.
Pharmaceuticals (Basel), 2017 Jan 31; 10(1). PMID: 28134851    Free PMC article.
Participation of the elderly population in clinical trials: barriers and solutions.
Aaron C Denson, Amit Mahipal.
Cancer Control, 2014 Jun 24; 21(3). PMID: 24955704
Platinum-based chemotherapy in advanced non-small-cell lung cancer: optimal number of treatment cycles.
Antonio Rossi, Massimo Di Maio.
Expert Rev Anticancer Ther, 2016 Mar 25; 16(6). PMID: 27010977
The role of comorbidities on the uptake of systemic treatment and 3-year survival in older cancer patients.
E P Stavrou, C Y Lu, N Buckley, S Pearson.
Ann Oncol, 2012 Feb 22; 23(9). PMID: 22351742
Disparities in quality of cancer care: The role of health insurance and population demographics.
Arti Parikh-Patel, Cyllene R Morris, Kenneth W Kizer.
Medicine (Baltimore), 2018 Feb 03; 96(50). PMID: 29390313    Free PMC article.
Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer.
Alan Sandler, Robert Gray, +5 authors, David H Johnson.
N Engl J Med, 2006 Dec 15; 355(24). PMID: 17167137
Highly Cited.
Crizotinib in ROS1-rearranged non-small-cell lung cancer.
Alice T Shaw, Sai-Hong I Ou, +18 authors, A John Iafrate.
N Engl J Med, 2014 Sep 30; 371(21). PMID: 25264305    Free PMC article.
Highly Cited.
Real-world practice patterns for patients with advanced non-small cell lung cancer: multicenter retrospective cohort study in Japan.
Hiroshi Isobe, Kiyoshi Mori, +6 authors, Terufumi Kato.
Lung Cancer (Auckl), 2017 Nov 11; 8. PMID: 29123433    Free PMC article.
Social differences in lung cancer management and survival in South East England: a cohort study.
Anders Berglund, Mats Lambe, +4 authors, Henrik Møller.
BMJ Open, 2012 May 29; 2(3). PMID: 22637374    Free PMC article.
Real-world chemotherapy treatment patterns in metastatic non-small cell lung cancer: Are patients undertreated?
Adrian G Sacher, Lisa W Le, +2 authors, Natasha B Leighl.
Cancer, 2015 Apr 22; 121(15). PMID: 25891153
Bevacizumab in Patients with Nonsquamous Non-Small Cell Lung Cancer and Asymptomatic, Untreated Brain Metastases (BRAIN): A Nonrandomized, Phase II Study.
Benjamin Besse, Sylvestre Le Moulec, +19 authors, Jean-Charles Soria.
Clin Cancer Res, 2015 Jan 24; 21(8). PMID: 25614446
Highly Cited.
A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER).
Yuankai Shi, Joseph Siu-Kie Au, +7 authors, Pan-Chyr Yang.
J Thorac Oncol, 2014 Jan 15; 9(2). PMID: 24419411    Free PMC article.
Highly Cited.
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.
Neal I Lindeman, Philip T Cagle, +10 authors, College of American Pathologists International Association for the Study of Lung Cancer and Association for Molecular Pathology.
J Mol Diagn, 2013 Apr 09; 15(4). PMID: 23562183
Highly Cited.
Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases.
R A Deyo, D C Cherkin, M A Ciol.
J Clin Epidemiol, 1992 Jun 01; 45(6). PMID: 1607900
Highly Cited.
Treatment variation by insurance status for breast cancer patients.
Natalie Coburn, John Fulton, +3 authors, Blake Cady.
Breast J, 2008 Mar 05; 14(2). PMID: 18315690
Do hospitals that serve a high percentage of Medicaid patients perform well on evidence-based guidelines for colon cancer care?
Kim F Rhoads, Justine V Ngo, +3 authors, R Adams Dudley.
J Health Care Poor Underserved, 2013 Aug 27; 24(3). PMID: 23974390
Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR.
Makoto Maemondo, Akira Inoue, +21 authors, North-East Japan Study Group.
N Engl J Med, 2010 Jun 25; 362(25). PMID: 20573926
Highly Cited.
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).
Pierpaolo Pastina, Valerio Nardone, +15 authors, Pierpaolo Correale.
Oncotarget, 2017 Nov 05; 8(44). PMID: 29100279    Free PMC article.
Barriers to Combined-Modality Therapy for Limited-Stage Small Cell Lung Cancer.
Todd A Pezzi, David L Schwartz, +7 authors, Stephen G Chun.
JAMA Oncol, 2018 Jan 06; 4(8). PMID: 29302695    Free PMC article.
Adjuvant chemotherapy uptake in non-small cell lung cancer.
Tallal Younis, Turki Al-Fayea, +2 authors, Nathalie Saint-Jacques.
J Thorac Oncol, 2008 Nov 04; 3(11). PMID: 18978562
The next frontier in non-small cell lung cancer: synergizing radiation therapy and immune checkpoint blockade.
Khinh Ranh Voong, Jarushka Naidoo, David S Ettinger.
Clin Adv Hematol Oncol, 2017 Sep 28; 15(8). PMID: 28949949
First-line crizotinib versus chemotherapy in ALK-positive lung cancer.
Benjamin J Solomon, Tony Mok, +13 authors, PROFILE 1014 Investigators.
N Engl J Med, 2014 Dec 04; 371(23). PMID: 25470694
Highly Cited.
Cancer-specific outcomes among young adults without health insurance.
Ayal A Aizer, Benjamin Falit, +8 authors, Paul L Nguyen.
J Clin Oncol, 2014 Jun 04; 32(19). PMID: 24888800    Free PMC article.
Palliative systemic therapy for advanced non-small cell lung cancer: Investigating disparities between patients who are treated versus those who are not.
Stephanie Y Brule, Khalid Al-Baimani, +5 authors, Paul Wheatley-Price.
Lung Cancer, 2016 May 31; 97. PMID: 27237022
Increasing Rates of No Treatment in Advanced-Stage Non-Small Cell Lung Cancer Patients: A Propensity-Matched Analysis.
Elizabeth A David, Megan E Daly, +6 authors, Robert J Canter.
J Thorac Oncol, 2017 Jan 23; 12(3). PMID: 28109804    Free PMC article.
EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII).
Anita Midha, Simon Dearden, Rose McCormack.
Am J Cancer Res, 2015 Nov 27; 5(9). PMID: 26609494    Free PMC article.
Highly Cited.
Pembrolizumab as first-line therapy for metastatic non-small-cell lung cancer.
Martin Reck.
Immunotherapy, 2017 Nov 18; 10(2). PMID: 29145737
Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer.
Giorgio Vittorio Scagliotti, Purvish Parikh, +17 authors, David Gandara.
J Clin Oncol, 2008 May 29; 26(21). PMID: 18506025
Highly Cited.
Adjuvant chemotherapy for non-small-cell lung cancer in the elderly: a population-based study in Ontario, Canada.
Sinead Cuffe, Christopher M Booth, +5 authors, Frances A Shepherd.
J Clin Oncol, 2012 Apr 25; 30(15). PMID: 22529258
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.
Vicki Leigh Keedy, Sarah Temin, +7 authors, Giuseppe Giaccone.
J Clin Oncol, 2011 Apr 13; 29(15). PMID: 21482992
Highly Cited.
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).
Qing Zhou, Yong Song, +13 authors, Yi-Long Wu.
BMC Cancer, 2017 Jul 05; 17(1). PMID: 28673332    Free PMC article.
Decreased early mortality associated with the treatment of acute myeloid leukemia at National Cancer Institute-designated cancer centers in California.
Gwendolyn Ho, Ted Wun, +5 authors, Theresa H M Keegan.
Cancer, 2018 Feb 17; 124(9). PMID: 29451695    Free PMC article.
Crizotinib versus chemotherapy in advanced ALK-positive lung cancer.
Alice T Shaw, Dong-Wan Kim, +20 authors, Pasi A Jänne.
N Engl J Med, 2013 Jun 04; 368(25). PMID: 23724913
Highly Cited.
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.
Amy P Abernethy, Ashwini Arunachalam, +4 authors, David P Carbone.
PLoS One, 2017 Jun 24; 12(6). PMID: 28644837    Free PMC article.
Cancer, Medicaid enrollment, and survival disparities.
Cathy J Bradley, Joseph Gardiner, Charles W Given, Caralee Roberts.
Cancer, 2005 Mar 16; 103(8). PMID: 15768435
Elderly patients' participation in clinical trials.
Premnath Shenoy, Anand Harugeri.
Perspect Clin Res, 2015 Dec 02; 6(4). PMID: 26623388    Free PMC article.
First-line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer.
Janette Greenhalgh, Kerry Dwan, +5 authors, John A Green.
Cochrane Database Syst Rev, 2016 May 26; (5). PMID: 27223332
Highly Cited. Systematic Review.
Stereotactic Radiation Therapy Augments Antigen-Specific PD-1-Mediated Antitumor Immune Responses via Cross-Presentation of Tumor Antigen.
Andrew B Sharabi, Christopher J Nirschl, +5 authors, Charles G Drake.
Cancer Immunol Res, 2014 Dec 21; 3(4). PMID: 25527358    Free PMC article.
Highly Cited.
Treatment Patterns and Overall Survival Associated with First-Line Systemic Therapy for Patients with Advanced Non-Small Cell Lung Cancer.
Michele M Spence, Rita L Hui, +3 authors, Nazia Rashid.
J Manag Care Spec Pharm, 2017 Jan 27; 23(2). PMID: 28125366
Trends in Cancer Survival by Health Insurance Status in California From 1997 to 2014.
Libby Ellis, Alison J Canchola, +3 authors, Scarlett Lin Gomez.
JAMA Oncol, 2017 Dec 02; 4(3). PMID: 29192307    Free PMC article.
Are there socio-economic inequalities in utilization of predictive biomarker tests and biological and precision therapies for cancer? A systematic review and meta-analysis.
Ruth P Norris, Rosie Dew, +4 authors, Adam Todd.
BMC Med, 2020 Oct 24; 18(1). PMID: 33092592    Free PMC article.
Systematic Review.
Real-life effectiveness of first-line anticancer treatments in stage IIIB/IV NSCLC patients: Data from the Czech TULUNG Registry.
Kristian Brat, Monika Bratova, +11 authors, Martin Svaton.
Thorac Cancer, 2020 Oct 06; 11(11). PMID: 33016001    Free PMC article.
Lung Cancer Stigma Then and Now: Continued Challenges Amid a Landscape of Progress.
Heidi A Hamann, Timothy J Williamson, Jamie L Studts, Jamie S Ostroff.
J Thorac Oncol, 2021 Jan 02; 16(1). PMID: 33384057    Free PMC article.