The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) have directed the care of patients with cancer for >20 years.1 In recent years, these guidelines have been further refined to include a category of “preferred” guideline treatment regimens to specify recommendations.2 Previous evaluations of NCCN Guidelines have focused on the use of specific, individual medications considered off-label or nonconcordant. In breast cancer, >10% of patients receive a medication not listed within the guidelines.3,4 These studies likely underestimate true levels of discordance because they do not capture concordance for regimens, which include specific single agents or combinations of hormone therapy, chemotherapy, and targeted therapies.
Use of nonconcordant treatments is known to contribute to the increasing cost of cancer care.5 The top 10 nonconcordant chemotherapy agents contribute to an estimated $2.5 billion in US cancer spending.6 Patient factors are known to contribute to nonconcordant care,4 but the role of provider factors is less clear. In an effort to minimize provider-based treatment variability, payers and health systems are implementing pathway programs restricting reimbursement for off-pathway regimens.7–10 Although these programs are showing early promise, few data exist about the outcomes for nonconcordant treatment regimens, particularly in metastatic breast cancer (MBC), in which treatment is heterogeneous and complex due to the large number of available guideline-based options. To ensure optimal patient care, it is essential to understand the types of commonly prescribed nonconcordant treatments and their impact on mortality, total Medicare costs, and rates of healthcare utilization.
The objectives of this study were to examine regimens concordant with NCCN Guidelines for MBC; describe categories of nonconcordant treatments; evaluate patient- and provider-level factors associated with nonconcordance; and determine the impact of nonconcordance on mortality, Medicare spending, and rates of healthcare utilization.
Dr. Rocque has disclosed that she receives grant/research support Genentech, Pfizer, Carevive, PackHealth, and Medscape, and is a consultant for Pfizer. The remaining authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
Dr. Rocque received funding for this study from the Walter B. Frommeyer, Jr. Fellowship in Investigative Medicine. This study used the linked SEER-Medicare database. Interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the NCI; the Office of Research, Development and Information, CMS; Information Management Services (IMS), Inc.; and the SEER Program tumor registries in the creation of the SEER-Medicare database.
Abstracts from this study were presented at the 2016 San Antonio Breast Cancer Symposium, December 6–10, 2016, and 2017 San Antonio Breast Cancer Symposium, December 5–9, 2017, San Antonio, Texas.
See JNCCN.org for supplemental online content.
EatonAASimaCSPanageasKS. Prevalence and safety of off-label use of chemotherapeutic agents in older patients with breast cancer: estimates from SEER-Medicare data. J Natl Compr Canc Netw2016;14:57–65.
HamelSMcNairDSBirkettNJ. Off-label use of cancer therapies in women diagnosed with breast cancer in the United States. Springerplus2015;4:209.
ShihYCGanzPAAberleD. Delivering high-quality and affordable care throughout the cancer care continuum. J Clin Oncol2013;31:4151–4157.
ContiRMBernsteinACVillaflorVM. Prevalence of off-label use and spending in 2010 among patent-protected chemotherapies in a population-based cohort of medical oncologists. J Clin Oncol2013;31:1134–1139.
ZonRTFrameJNNeussMN. American Society of Clinical Oncology policy statement on clinical pathways in oncology. J Oncol Pract2016;12:261–266.
NeubauerMAHovermanJRKolodziejM. Cost effectiveness of evidence-based treatment guidelines for the treatment of non-small-cell lung cancer in the community setting. J Oncol Pract2010;6:12–18.
HovermanJRCartwrightTHPattDA. Pathways, outcomes, and costs in colon cancer: retrospective evaluations in 2 distinct databases. Am J Manag Care2011;17(Suppl 5):SP45–52.
KlabundeCNPotoskyALLeglerJMWarrenJL. Development of a comorbidity index using physician claims data. J Clin Epidemiol2000;53:1258–1267.
CharlsonMEPompeiPAlesKLMacKenzieCR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis1987;40:373–383.
DeyoRACherkinDCCiolMA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol1992;45:613–619.
SchwentnerLWockelAKonigJ. Adherence to treatment guidelines and survival in triple-negative breast cancer: a retrospective multi-center cohort study with 9,156 patients. BMC Cancer2013;13:487.
WockelAKurzederCGeyerV. Effects of guideline adherence in primary breast cancer—a 5-year multi-center cohort study of 3976 patients. Breast2010;19:120–127.
DenuRAHamptonJMCurreyA. Influence of patient, physician, and hospital characteristics on the receipt of guideline-concordant care for inflammatory breast cancer. Cancer Epidemiol2016;40:7–14.
CarrickSParkerSWilckenN. Single agent versus combination chemotherapy for metastatic breast cancer. Cochrane Database Syst Rev2005:CD003372.
CarrickSParkerSThorntonCE. Single agent versus combination chemotherapy for metastatic breast cancer. Cochrane Database Syst Rev2009:CD003372.
DearRFMcGeechanKJenkinsMC. Combination versus sequential single agent chemotherapy for metastatic breast cancer. Cochrane Database Syst Rev2013:CD008792.
New NCCN Guidelines include evidence blocks to illustrate value in breast, colon, kidney, and rectal cancers. J Natl Compr Canc Netw2016;14:xxxiv–xxxv.
FeinbergBALangJGrzegorczykJ. Implementation of cancer clinical care pathways: a successful model of collaboration between payers and providers. J Oncol Pract2012;8(3 Suppl):e38s–43s.
KreysEDKoellerJM. Documenting the benefits and cost savings of a large multistate cancer pathway program from a payer's perspective. J Oncol Pract2013;9:e241–247.