Cost-Effectiveness Analysis of Tyrosine Kinase Inhibitors for Patients with Advanced Gastrointestinal Stromal Tumors.
BACKGROUND
The management of advanced gastrointestinal stromal tumors (GISTs) has been modified considerably by the availability of costly tyrosine kinase inhibitors (TKIs); however, the best therapeutic sequence in terms of cost and effectiveness remains unknown.


OBJECTIVE
The aim of this study was to compare four potential strategies (reflecting the potential daily practice), each including imatinib 400 mg/day, as first-line treatment: S1 (imatinib400/best supportive care [BSC]); S2 (imatinib400/imatinib800/BSC); S3 (imatinib400/sunitinib/BSC); and S4 (imatinib400/imatinib800/sunitinib/BSC).


METHODS
A Markov model was developed with a hypothetical cohort of patients and a lifetime horizon. Transition probabilities were estimated from the results of clinical trials. The analysis was performed from the French payer perspective, and only direct medical costs were included. Clinical and economic parameters were discounted, and the robustness of results was assessed.


RESULTS
The least costly and effective strategy was S1, at a cost of €65,744 for 32.9 life months (reference). S3 was the most cost-effective strategy, with an incremental cost-effectiveness ratio (ICER) of €48,277/life-year saved (LYS). S2 was dominated, and S4 yielded an ICER of €363,320/LYS compared with S3. Sensitivity analyses confirmed the robustness of these results; however, when taking into account a price reduction of 80 % for imatinib, S2 and S4 become the most cost-effective strategies.


CONCLUSIONS
Our approach is innovative to the extent that our analysis takes into account the sequential application of TKIs. The results suggest that the S1 strategy is the best cost-effective strategy, but a price reduction of imatinib impacts on the results. This approach must continue, including new drugs and their impact on the quality of life of patients with advanced GISTs.
Department of Pharmacy, University Hospital, Boulevard Fleming, 25030, Besançon Cedex, France. v1nerich@chu-besancon.fr.|University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions hôte-greffon-tumeur - Ingénierie Cellulaire et Génique, Besançon, France. v1nerich@chu-besancon.fr.
Virginie
V
Nerich
Department of Pharmacy, University Hospital, Boulevard Fleming, 25030, Besançon Cedex, France.
Camille
C
Fleck
Department of Medical Oncology, University Hospital, Besançon, France.
Loïc
L
Chaigneau
Department of Medical Oncology, Centre Georges François Leclerc, Dijon, France.
Nicolas
N
Isambert
University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions hôte-greffon-tumeur - Ingénierie Cellulaire et Génique, Besançon, France.|Department of Medical Oncology, University Hospital, Besançon, France.
Christophe
C
Borg
Department of Medical Oncology, University Hospital, Besançon, France.
Elsa
E
Kalbacher
Department of Medical Oncology, University Hospital, Besançon, France.
Marine
M
Jary
Department of Pediatry, University Hospital, Besançon, France.
Pauline
P
Simon
University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions hôte-greffon-tumeur - Ingénierie Cellulaire et Génique, Besançon, France.|Department of Medical Oncology, University Hospital, Besançon, France.
Xavier
X
Pivot
Department of Medicine, Centre Léon Bérard, Lyon, France.|University Claude Bernard, Lyon, France.|French Sarcoma Group (GSF-GETO), Paris, France.|European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium.
Jean-Yves
JY
Blay
Department of Pharmacy, University Hospital, Boulevard Fleming, 25030, Besançon Cedex, France.|University Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions hôte-greffon-tumeur - Ingénierie Cellulaire et Génique, Besançon, France.
Samuel
S
Limat
D017281:Cost of Illness; D003362:Cost-Benefit Analysis; D016527:Drug Costs; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D008390:Markov Chains; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011758:Pyrroles / Q000627:therapeutic use; D011788:Quality of Life; D000077210:Sunitinib
D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib
Lancet Oncol. 2013 Nov;14 (12 ):1175-82
24140183
Bull Acad Natl Med. 2012 Apr-May;196(4-5):861-74; discussion 874-76
23550449
J Clin Oncol. 2008 Feb 1;26(4):626-32
18235122
Eur J Cancer. 2008 May;44(7):972-7
18372169
Clin Transl Oncol. 2008 Dec;10 (12 ):831-9
19068454
J Clin Oncol. 2007 Mar 20;25(9):1107-13
17369574
Value Health. 2014 Jan-Feb;17(1):5-14
24438712
J Med Econ. 2010;13(4):681-90
21067355
J Clin Oncol. 2012 Jul 1;30(19):2401-7
22614970
Hum Pathol. 2002 May;33(5):466-77
12094371
Am J Med. 1982 Dec;73(6):883-8
7148881
Target Oncol. 2012 Dec;7(4):227-31
22249657
BMC Cancer. 2011 Feb 15;11:72
21324142
Gastric Cancer. 2015 Jul;18(3):627-34
24957256
N Engl J Med. 2002 Aug 15;347(7):472-80
12181401
Med Decis Making. 1994 Jan-Mar;14(1):52-8
8152357
Health Technol Assess. 2005 Jul;9(25):1-142
15985189
Clin Drug Investig. 2007;27(2):85-93
17217313
Leuk Lymphoma. 2015;56(8):2315-25
25393806
J Oncol Pharm Pract. 2008 Sep;14(3):105-12
18524863
Lancet. 2013 Jan 26;381(9863):295-302
23177515
Cancer. 2015 May 1;121(9):1405-13
25641662
Cancer. 2011 Oct 15;117(20):4633-41
21456006
Ann Oncol. 2012 Jul;23 (7):1680-7
22357255
Eur J Cancer. 2006 May;42(8):1093-103
16624552
Ann Oncol. 2014 Sep;25 Suppl 3:iii21-6
25210085
J Clin Oncol. 2010 Mar 1;28(7):1247-53
20124181
Bull Cancer. 2010 Mar;97(3):E16-22
20129875
BMJ. 2007 Aug 25;335(7616):358-9
17717337
Lancet. 2006 Oct 14;368(9544):1329-38
17046465
Clin Cancer Res. 2012 Jun 1;18(11):3170-9
22661587
Lancet. 2001 Oct 27;358(9291):1421-3
11705489
Am J Med. 1982 Dec;73(6):889-97
6983298
Ann Oncol. 2013 Apr;24(4):1087-93
23175622
Eur J Cancer. 2005 Aug;41(12):1751-7
16098458
Br J Cancer. 2008 Jun 3;98 (11):1762-8
18506179