Pharmacologic Costs of Tyrosine Kinase Inhibitors in First-Line Therapy for Advanced Non–Small-Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations: A Review of Pivotal Phase III Randomized Controlled Trials

Abstract

Many driver mutations that determine the malignant behavior of lung cancer have been identified in recent years. 1 Lazarus D.R. Ost D.E. How and when to use genetic markers for nonsmall cell lung cancer. Curr Opin Pulm Med. 2013; 19: 331-339 PubMed Google Scholar The epidermal growth factor receptor (EGFR) signaling pathway is crucial for regulating tumorigenesis and cell survival and could be important in the development and progression of non–small-cell lung cancer (NSCLC). 2 Lee C.K. Brown C. Gralla R.J. et al. Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. J Natl Cancer Inst. 2013; 105: 595-605 Crossref PubMed Scopus (444) Google Scholar Activating mutation in exons 19 or 21 of EGFR in NSCLC are associated with increased sensitivity to EGFR tyrosine kinase inhibitors (TKIs). 3 Besse B. Adjei A. Baas P. et al. 2nd ESMO consensus conference on lung cancer: non-small-cell lung cancer first-line/second and further lines of treatment in advanced disease. Ann Oncol. 2014; 25: 1475-1484 Crossref PubMed Scopus (198) Google Scholar The second European Society for Medical Oncology Consensus Conference on Lung Cancer 3 Besse B. Adjei A. Baas P. et al. 2nd ESMO consensus conference on lung cancer: non-small-cell lung cancer first-line/second and further lines of treatment in advanced disease. Ann Oncol. 2014; 25: 1475-1484 Crossref PubMed Scopus (198) Google Scholar has recommended that an EGFR TKI is the preferred first-line treatment for patients with EGFR-mutated NSCLC (strength of recommendation, A; level of evidence, I), as demonstrated by several randomized trials, with a superior response rate and progression-free survival (PFS) and better quality of life scores compared with combination chemotherapy in the first-line setting. The advent of new targeted agents has inevitably placed the focus on the sustainability of the National Health Service systems. The financial burden of cancer care has more than doubled in the past decade, 4 Elkin E.B. Bach P.B. Cancer's next frontier: addressing high and increasing costs. JAMA. 2010; 303: 1086-1087 Crossref PubMed Scopus (133) Google Scholar resulting in an increased focus on cancer therapies that are both efficacious and cost-effective. 5 Cohn D.E. Kim K.H. Resnick K.E. O'Malley D.M. Straughn Jr., J.M. At what cost does a potential survival advantage of bevacizumab make sense for the primary treatment of ovarian cancer? A cost-effectiveness analysis. J Clin Oncol. 2011; 29: 1247-1251 Crossref PubMed Scopus (150) Google Scholar Medical oncologists directly or indirectly control or influence most cancer care costs, including the use and choice of drugs. An emerging issue is to understand how a survival gain can justify an inevitable increase in costs. In the United Kingdom, the National Institute for Health and Care Excellence evaluates the clinical effectiveness and cost-effectiveness of oncology interventions, explicitly considering the cost per the quality-adjusted life-year gained, and provides the National Health Service with advice on which treatments should be covered. 6 Smith T.J. Hillner B.E. Bending the cost curve in cancer care. N Engl J Med. 2011; 364: 2060-2065 Crossref PubMed Scopus (329) Google Scholar From a societal perspective, the total spending on cancer care is driven by the cost to treat an individual patient and the number of patients treated. In general, increases in the cost of health care are driven by innovation, and, in the case of cancer care, innovation can take many forms, such as new drugs or established drugs with new indications. However, doing more for patients does not always equate to spending more. When used selectively, novel interventions can save money. 6 Smith T.J. Hillner B.E. Bending the cost curve in cancer care. N Engl J Med. 2011; 364: 2060-2065 Crossref PubMed Scopus (329) Google Scholar , 7 Sullivan R. Peppecorn J. Sikora K. et al. Delivering affordable cancer care in high-income countries. Lancet Oncol. 2011; 12: 933-980 Abstract Full Text Full Text PDF PubMed Scopus (536) Google Scholar , 8 Drummond M.F. Mason A.R. European perspective on the costs and cost-effectiveness of cancer therapies. J Clin Oncol. 2007; 25: 191-195 Crossref PubMed Scopus (105) Google Scholar , 9 Sarin R. Criteria for deciding cost-effectiveness for expensive anti-cancer agents. J Cancer Res Ther. 2008; 4: 1-2 Crossref PubMed Scopus (33) Google Scholar