Highlights
- •Oral drugs benefit patients with EGFR+ and ALK+ positive advanced lung cancer.
- •Approximately 18% of EGFR+ and ALK+ positive patients do not receive oral drugs.
- •Patients diagnosed in later years were less likely to receive oral drugs.
- •Underuse of EGFR and ALK oral drugs is associated with inferior survival.
- •Oncology providers need to identify and address access barriers to oral drugs.
Abstract
Introduction
We assessed the proportion of patients with advanced epidermal growth factor receptor
(EGFR) and anaplastic lymphoma kinase (ALK) positive non–small-cell lung cancer (NSCLC) who receive tyrosine kinase inhibitors
(TKIs) in the real-world, predictors of TKI use, and impact of TKI therapy on overall
survival (OS).
Materials and Methods
We identified patients diagnosed with stage IV EGFR+ and ALK+ positive NSCLC from January 1, 2010 to December 31, 2018, in the Cancer Surveillance
System registry and linked their records to Medicare and commercial insurance claims.
We reported the proportions of patients with 1 or more TKI claims versus no TKI claims
and used logistic regression to identify predictors of TKI use. We evaluated the effect
of TKI use on OS by applying extended Cox proportional hazard models with TKI use
as a time-dependent exposure and landmark analysis in a subcohort (N = 105). We adjusted
Cox models for confounding patient characteristics.
Results
Of 117 eligible patients (median age = 69; 62% women; 88% EGFR+), 21 (17.9%) had no TKI claims. Diagnosis in 2015 to 2018 was independently associated
with lower likelihood of TKI therapy compared with 2010 to 2014 (adjusted odds ratio,
0.29; P = .020). TKI use was associated with longer OS in a multivariate extended Cox model
and in the landmark analysis (adjusted hazard ratio [HR], 0.58; 95% confidence interval
[CI], 0.33; 0.99; P = .048; adjusted HR, 0.55; 95% CI, 0.30; 1.00; P = .050).
Conclusion
Approximately 18% of patients with advanced EGFR+ and ALK+ positive NSCLC do not receive TKIs and have inferior survival. Further studies need
to investigate barriers of access to TKIs in biomarker-selected patients.
Keywords
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 accessOne-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 CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.N Engl J Med. 2009; 361: 947-957
- Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial.Lancet Oncol. 2010; 11: 121-128
- Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR.N Engl J Med. 2010; 362: 2380-2388
- First-SIGNAL: first-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung.J Clin Oncol. 2012; 30: 1122-1128
- Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations.J Clin Oncol. 2013; 31: 3327-3334
- Crizotinib versus chemotherapy in advanced ALK-positive lung cancer.N Engl J Med. 2013; 368: 2385-2394
- First-line crizotinib versus chemotherapy in ALK-positive lung cancer.N Engl J Med. 2014; 371: 2167-2177
- NCCN Guidelines Insights: non-small cell lung cancer, version 5.2018.J Natl Compr Canc Netw. 2018; 16: 807-821
- Molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: American Society of Clinical Oncology Endorsement Summary of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Clinical Practice Guideline Update.J Oncol Pract. 2018; 14: 323-327
- 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.J Thorac Oncol. 2018; 13: 323-358
- Genomic profiling of advanced non-small cell lung cancer in community settings: gaps and opportunities.Clin Lung Cancer. 2017; 18: 651-659
- Quality in the age of precision medicine: the clinician perspective.J Oncol Pract. 2016; 12: 839-843
- Challenges in molecular testing in non-small-cell lung cancer patients with advanced disease.Lancet. 2016; 388: 1002-1011
- Exploration of PCORnet data resources for assessing use of molecular-guided cancer treatment.JCO Clin Cancer Inform. 2020; 4: 724-735
- Precision Medicine in Oncology II: economics of targeted agents and immuno-oncology drugs.J Clin Oncol. 2020; 38: 351-358
- Specialty pharmacy services for patients receiving oral medications for solid tumors.Am J Health Syst Pharm. 2016; 73: 775-796
- Pharmaceutical assistance programs for cancer patients in the era of orally administered chemotherapeutics.J Oncol Pharm Pract. 2018; 24: 424-432
- Use of charity financial assistance for novel oral anticancer agents.J Oncol Pract. 2018; 14: e221-e228
- Molecular testing turnaround time in non-small-cell lung cancer: monitoring a moving target.Clin Lung Cancer. 2018; 19: e589-e590
- Broad-based molecular testing for lung cancer: precisely the time for precision.JAMA. 2018; 320: 445-446
- Real-world management of patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer in the USA.PLoS One. 2019; 14e0209709
- Association of patient characteristics and tumor genomics with clinical outcomes among patients with non-small cell lung cancer using a Clinicogenomic database.JAMA. 2019; 321: 1391-1399
- 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: 86-92
- Cost effectiveness of multigene panel sequencing for patients with advanced non-small-cell lung cancer.JCO Clin Cancer Inform. 2019; 3: 1-10
- Characterizing potentially preventable cancer- and chronic disease-related emergency department use in the year after treatment initiation: a regional study.J Oncol Pract. 2018; 14: e176-e185
Fred Hutchinson Cancer Research Center. Cancer Surveillance System (CSS). Available at: https://www.fredhutch.org/en/research/divisions/public-health-sciences-division/research/epidemiology/cancer-surveillance-system.html. Accessed on October 23, 2020.
- Validity of natural language processing for ascertainment of EGFR and ALK test results in seer cases of stage IV non-small-cell lung cancer.JCO Clin Cancer Inform. 2019; 3: 1-15
- A refined comorbidity measurement algorithm for claims-based studies of breast, prostate, colorectal, and lung cancer patients.Ann Epidemiol. 2007; 17: 584-590
- Challenges of guarantee-time bias.J Clin Oncol. 2013; 31: 2963-2969
- Immortal time bias in observational studies of time-to-event outcomes: assessing effects of postmastectomy radiation therapy using the National Cancer Database.Cancer Control. 2018; 251073274818789355
- Time-dependent covariates in the Cox proportional-hazards regression model.Annu Rev Public Health. 1999; 20: 145-157
- Statins associate with improved mortality among patients with certain histological subtypes of lung cancer.Lung Cancer. 2018; 126: 89-96
- Immortal time bias: a frequently unrecognized threat to validity in the evaluation of postoperative radiotherapy.Int J Radiat Oncol Biol Phys. 2012; 83: 1365-1373
- Association of broad-based genomic sequencing with survival among patients with advanced non-small cell lung cancer in the community oncology setting.JAMA. 2018; 320: 469-477
- Trends in the cost and use of targeted cancer therapies for the privately insured nonelderly: 2001 to 2011.J Clin Oncol. 2015; 33: 2190-2196
- Rising prices of targeted oral anticancer medications and associated financial burden on Medicare beneficiaries.J Clin Oncol. 2017; 35: 2482-2489
- Impact of cost sharing on specialty drug utilization and outcomes: a review of the evidence and future directions.Am J Manag Care. 2016; 22: 188-197
- High cost sharing and specialty drug initiation under Medicare Part D: a case study in patients with newly diagnosed chronic myeloid leukemia.Am J Manag Care. 2016; 22: s78-s86
- Drug pricing trends for orally administered anticancer medications reimbursed by commercial health plans, 2000-2014.JAMA Oncol. 2016; 2: 960-961
- Specialty drug pricing and out-of-pocket spending on orally administered anticancer drugs in Medicare Part D, 2010 to 2019.JAMA. 2019; 321: 2025-2027
- Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs.JAMA. 2014; 311: 1998-2006
- Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer.N Engl J Med. 2018; 378: 113-125
- Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study.Ann Oncol. 2020; 31: 1056-1064
- Brigatinib versus crizotinib in advanced ALK inhibitor-naive ALK-positive non-small cell lung cancer: second interim analysis of the phase III ALTA-1L trial.J Clin Oncol. 2020; 38: 3592-3603
Article info
Publication history
Published online: February 03, 2021
Accepted:
January 28,
2021
Received in revised form:
January 19,
2021
Received:
November 4,
2020
Identification
Copyright
Published by Elsevier Inc.
