Economic Burden of Toxicities Associated with Treating Metastatic Melanoma in the United States.
BACKGROUND
Little has been reported on the costs of managing the adverse events (AEs) associated with current therapies for patients with regional or distant metastatic melanoma.


OBJECTIVE
To identify treatment-related AEs in patients with metastatic melanoma and to estimate the associated costs of treating these AEs in the United States.


METHODS
A cost-estimation study for AEs associated with treatment of metastatic melanoma was conducted from 2012 to 2013 by identifying grades 3 and 4 AEs through the use of a comprehensive search of drug labels and English-language, published phase 2/3 studies in PubMed, conference abstracts, and the National Comprehensive Cancer Network guidelines. Resource utilization for the management of each type of AE in the outpatient setting was obtained via interviews with 5 melanoma specialists in the United States. Unit costs for an AE associated with melanoma treatment in the outpatient setting were assigned using Medicare reimbursement rates to obtain these costs. Hospitalization and length-of-stay costs were estimated for each associated AE using the large national claims database Optum Clinformatics Data Mart for the period of July 1, 2004, to November 30, 2012.


RESULTS
The most common AEs associated with chemotherapies used for melanoma were neutropenia, vomiting, and anemia. The most common AEs associated with vemurafenib were cutaneous squamous-cell carcinoma or keratoacanthoma, rash, and elevated liver enzymes; the most common AEs associated with dabrafenib were cutaneous squamous-cell carcinoma and pyrexia. Trametinib was most often associated with hypertension and rash. The most common AEs with ipilimumab were immune-related diarrhea or colitis, dyspnea, anemia, vomiting, and, less frequently, hypophysitis. The most common grade 3/4 AE with talimogene laherparepvec was cellulitis. The highest treatment costs for an AE in the outpatient setting were for neutropenia ($2092), headache ($609), and peripheral neuropathy ($539). The highest mean inpatient costs for an AE were for acute myocardial infarction, sepsis, and coma, which ranged from $31,682 to $47,069. Colitis or diarrhea, cutaneous squamous-cell carcinoma, thrombocytopenia, hyponatremia, oliguria or anuria, hypertension, anemia, and elevated liver enzymes were associated with mean costs for hospitalization ranging from $19,122 to $26,861.


CONCLUSIONS
The costs of managing treatment-related AEs in patients with metastatic melanoma are substantial. Effective treatments with improved safety profiles may help to reduce these costs. Until real-world evidence for the costs associated with treatment toxicity is available in the outpatient and inpatient settings, the costs estimated in this study can help inform decision makers about the cost-effectiveness of managing patients with metastatic melanoma.
Director, Health Economics and Outcomes Research, IMS Health, San Francisco, CA.
S Pinar
SP
Bilir
Senior Manager, Amgen, Thousand Oaks, CA.
Qiufei
Q
Ma
Director, Amgen.
Zhongyun
Z
Zhao
Senior Consultant, Health Economics and Outcomes Research, IMS Health, Plymouth Meeting, PA.
Elizabeth
E
Wehler
General Manager, Medical and Scientific Services, Health Economics and Outcomes Research, IMS Health, San Francisco.
Julie
J
Munakata
Executive Director, Amgen.
Beth
B
Barber
adverse events; chemotherapy; cost analysis; cost of illness; dabrafenib; dacarbazine; drug-related side effects; interleukin-2; ipilimumab; metastatic melanoma; talimogene laherparepvec; temozolomide; toxicities; trametinib; vemurafenib
N Engl J Med. 2012 Feb 23;366(8):707-14
22356324
J Clin Oncol. 2015 Sep 1;33(25):2780-8
26014293
N Engl J Med. 2012 Jul 12;367(2):107-14
22663011
N Engl J Med. 2010 Aug 19;363(8):711-23
20525992
J Transl Med. 2012 Jul 09;10:85
22554099
Melanoma Res. 2015 Aug;25(4):312-20
25882026
Invest New Drugs. 2011 Jun;29(3):489-98
20082117
N Engl J Med. 2011 Jun 30;364(26):2507-16
21639808
J Manag Care Spec Pharm. 2015 Feb;21(2):158-64
25615005
N Engl J Med. 2015 Jan 1;372(1):30-9
25399551
Am Health Drug Benefits. 2016 Jun;9(4):203-13
27688833
N Engl J Med. 2011 Jun 30;364(26):2517-26
21639810
J Clin Oncol. 2007 Sep 1;25(25):3802-7
17761969
Melanoma Res. 2012 Dec;22(6):454-9
22990665
Lancet. 2012 Jul 28;380(9839):358-65
22735384
Eur J Cancer. 2011 Jul;47(10):1476-83
21600759
N Engl J Med. 2015 Jul 2;373(1):23-34
26027431