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COST ANALYSIS OF 3-YEARS FOLLOW-UP
OF A TRASTUZUMAB TREATED COHORT
K. Le Lay (1), M. Devaux (1), C. Tsé (2), D. Brault (2), J.P. Lotz (2), R. Launois (1,3)
1 : Réseau d’Evaluation d’Economie de la Santé (REES France), 28, rue d’Assas, 75006 Paris - 2 : Hôpital Tenon , 4, rue de Chine,
75970 Paris Cedex 20 – 3 : Université Paris XIII- Faculté de médecine, 74, rue Marcel Cachin , 93 017 Bobigny Cedex
INTRODUCTION
Trastuzumab therapy initiated since august 2000 in 25% of the Metastatic Breast Cancer (MBC) patients over-expressing HER2. The
product is licenced in monotherapy for patients pre-treated with anthracyclines and taxanes, or associated with paclitaxel for patients who
can not be pre-treated by anthracyclines. Trastuzumab is an anti-HER2 monoclonal antibody immunotherapy. The French Ministry of
health funded the HER.ME.S study started in 2001 to evaluate the economic impact of a targeted therapy.
OBJECTIVES
To evaluate the economic impact of trastuzumab treatment in MBC and to determinate the prediction level of the HER2 Extra-Cellular
Domain (H-ECD) rate on the 2-months treatment response using correlations.
METHODS
HER.ME.S (HERceptin/Métastatique/Sein) Study :
A clinical, biochemical and pharmaco-economic study : Prospective and multicentric
trial. Clinical data were collated on line by 11 centers : 7 AP-HP (public assistance and
hospitals of Paris) and 4 CRLCC (regional centers of fight against cancer).
Table 1 : Four Protocols
Designation
Treatment Schedule
T1
-100%
T3
Between -100% and -30%
TP1
Between -30% and +20%
TP3
> 20%
Only HER2 3+ or 2+ and FISH+ patients received treatment
Time to recruitment is 36 months, and in theory the follow-up time is 2 years
The 2-months treatment response is evaluated according to RECIST criteria.
Table 2 : RECIST criteria
Response
Pre-inclusion Biochemical Methods
• IHC (Immuno-HistoChemistry) test determinates the HER2 status.
• When HER2 status is 2+, HER2/neu amplification has to be evaluated by the FISH
(Hybridation In Situ par Fluorescence) method.
• The H-ECD level is measured by ELISA (Enzyme Linked ImmunoSorban Assay)
technique.
Statistical Methods
• Survival Analysis : Overall Survival, Time to Tumour Progression, Time to
Treatment Failure, Progression Free Survival (Kaplan-Meier Method, log-rank test)
• ITT Analysis : TP1 versus TP3, test of comparison of means, Wilcoxon test and
Khi-2 test.
• Correlations : Relative risk, McNemar test, Kappa
Economic Analysis :
Evolution of the sum of the longest
diameters of the target lesion
Complete
-100%
Partial
Between -100% and -30%
Stable
Between -30% and +20%
Progression
> 20%
The 2-months response is compared to H-ECD level at baseline and after 2 months.
• Overall patient management cost includes pre-inclusion screening cost and treatment
cost.
• Treatment cost was calculated by adding DRG costs (2004) and onerous drug
reimbursed over DRGs.
• Drugs acquisition and biological and radiological examinations components were
replaced by molecular real costs (prices AP-HP and CRLCC from 2001 to 2004) and
by the costs of biological, cardiac and tumour volume assessments and IHC and FISH
methods from NGAP 2004 (general nomenclature of the professional acts).
RESULTS
In a 3-years follow-up period, 120 patients were pre-included and
88 received trastuzumab treatment :
• Average age : 54 years [25-75].
• Median time to treatment: 30,3 weeks [25-35].
81 patients dropped out :
• 54 for progression,
• 12 for cardiac toxicities,
• 3 for neurological toxicities,
• 5 because of patient will,
• 5 for other reasons,
• 2 for death.
Diagram 1 : Overall Patient Management Cost
(n=120) on 36 weeks : € 4.178.000
Onerous Drugs
Acquisition
71%
Hospitalizations
22%
Pre-inclusions
Assessments
2%
Assessments
5%
41 patients out of 88 died : 40 after progression and 1 after an infection.
Overall Survival : 60 weeks [48-80].
Time to Tumour Progression : 34 weeks [27-43].
Diagram 2 : Treatment Average Cost per Patient (n=88) all
treatment confused on 36 weeks : € 46.345
Onerous Drugs
Acquisition
72%
ITT analysis : 62 patients received TP1, 25 TP3 and 1 T1. No
statistically significant difference between TP1 and TP3.
Correlation analysis established on 27 patients : risk 2.2 times higher
to have a 2-months progression response for patients whose H-ECD level
increases between 0 and 2 months, compared to patients whose H-ECD
level decreases.
T umor volume
assessments
1%
Cardiac
assessments
3%
Pre-inclusion Screening Average Cost : € 829 per patient.
Administration
23%
Laboratory
assessments
1%
CONCLUSION
From an economic perspective, HER2 assays are cost effective : they are less expensive than cytotoxic and/or trastuzumab .
REFERENCES
CONTACT
Baselga J, Tripathy D, Mendelsohn J et al.: Phase II study of weekly intravenous trastuzumab (Herceptin) in patients with HER/neuoverexpressing metastatic breast cancer. Semin Oncol 1999, Suppl 4, 12 : 78-83. Slamon D, Leyland-Jones B, Shak S, et al. Use of
chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpress HER2. New Eng J Med, 2001, 344,
11 : 783-92 et Addition of Herceptin (humanized anti-HER2 antibody) to first line chemotherapy for HER2 overexpressing breast cancer
markedly increased anticancer activity: A randomized multinational controlled phase III trial: Proc Am Soc Clin Oncol 1998; 17: 98. Le
Lay K., Lotz J.P., Launois R : Création d’une Base de données Intranet AP-HP et CRLCC dans le cadre du Programme 2000 de Soutien
des Innovations Diagnostiques et Thérapeutiques Coûteuses. Eurocancer Juillet 2002, Paris.
REES France
POS-5171/05
ISPOR 8th annual European congress
Réseau d’Évaluation en Économie de la Santé
28, rue d’Assas – 75006 Paris, France
Tel: +33 1 44 39 16 90 – Fax: + 33 1 44 39 16 92
E-mail: [email protected]
Web: www.rees-france.com
6-8 November 2005, Palazzo Degli Affari, Florence, Italy
Poster Session I