Trastuzumab for breast cancer treatment

AUGUSTOVSKI, F; PICHON-RIVIERE A,; ALCARAZ A; BARDACH, ARIEL; FERRANTE, D; GARCIA MARTÍ, SEBASTIAN; GLUJOVSKY, D; LOPEZ, A; REGUEIRO, A

Documentos de Evaluación de Tecnologías Sanitarias

IECS

Año: 2005 p. 1 - 30

1668-2793

This report is intended to assess the usefulness of trastuzumab in breast cancer treatment and determine its valid indications.A search was started on the main literature databases (MEDLINE, Cochrane, DARE, LILACS, NHS, NICE, EMBASE), on the Internet's general search engines, health technology assessment agencies and health sponsors.Trastuzumab efficacy on metastatic disease:As second line or subsequent treatment: A Phase II study assessed the efficacy of trastuzumab in 222 women with metastatic disease and HER-2/neu overexpression after one or more chemotherapy treatments. The complete response rate was 15% with a median survival of 13 months, median to progression of 3.1 months and median response duration of 9.1 months. As first line monotherapy: A Phase II study which included 114 patients with metastatic breast cancer with HER2 overexpression who received first line trastuzumab treatment found that the objective response rate (complete or partial response) was 26% (CI 95% 18.2 to 34.4%), lower than the response achieved with standard first line schemes.As first line in combination with other chemotherapy agents: A study randomly assigned 234 patients to receive standard chemotherapy alone and 235 patients to receive standard chemotherapy plus trastuzumab. The addition of trastuzumab to the chemotherapy treatment was associated with an increase in median time to disease progression (7.4 vs 4.6 months; p<0.001), a greater rate of objective response (50% vs. 32%; p< 0.001), a greater response duration (9.1 vs. 6.1 months), a lower mortality rate at one year (22% vs. 33%, p=0.008), a greater median survival (25.1 vs 20.3 months, p=0.046) and a 20% death risk reduction.Trastuzumab efficacy in surgical invasive breast cancer:As neoadjuvant therapy (prior to surgery): A randomized study included patients with surgical, invasive, stage II or IIIA, HER2 positive breast cancer to receive paclitaxel followed by 5-fluorouracil + epirubicin + cyclophosphamide or the same scheme associated to weekly trastuzumab for 24 weeks, prior to surgery. The study was discontinued with 42 patients due to superiority of the second treatment modality: the rate of pathologic complete remission (disappearance of all residual invasive cancer from the breast or axilla) was 26.3% for chemotherapy alone and 65.2% for chemotherapy in combination with trastuzumab.As adjuvant therapy (post-surgery): In a joint interim analysis of both studies which included patients with positive HER2 who had positive lymph nodes or high risk negative lymph nodes, 3,676 patients were randomized after surgery to receive doxorubicin, cyclophosphamide and paclitaxel or the same regimen plus 52 weeks of trastuzumab. The occurrence of the combined endpoint of recurrence, second primary cancer or death after recurrence took place most frequently in the control groups than in the trastuzumab groups: 261 vs. 133 event with a HR of 0.48 with p<0.001. The mean follow-up was 2 years. The percentage of disease-free patients at 3 years was 75.4% in the control group and 87.1% the trastuzumab group, with an absolute difference of 11.8% (CI 95% 8.1 to 15.4). At 4 years, the percentages were 67.1% and 85.3% respectively, and the absolute difference was 18.2% (CI 95% 12.7 to 23.7). There were 62 deaths in the trastuzumab group and 92 the control group (HR 0.67 with a CI95% 0.48 to 0.93, p=0.015). Similar results were reported in the interim analysis of the HERA study with 5090 patients.Safety profile The most serious adverse event is heart dysfunction, which worsens when trastuzumab is associated with anthracyclines. Trastuzumab is associated with rates of heart dysfunction of 2 to 13%, increasing to 27% when anthracyclines are added, especially doxorubicin.Suppliers and health technology assessment agencies: There is consensus among technology evaluations and coverage policies of the NHS Centre for Reviews and Dissemination of York University and the National Horizon Scanning Centre of Birmingham University, United Kingdom, and BlueCross BlueShield from Tennessee and Aetna from United States, about the efficacy of trastuzumab in the treatment of metastatic breast tumors that have HER2 overexpression as second line monotherapy and subsequent treatment or as first line combined with taxanes. Most of them were carried out before the publication of the interim analysis of studies which evaluate trastuA cost-effectiveness study carried out by the European Oncology Society in patients with metastatic breast cancer with HER2 overexpression found a life-year gained range between 0.3 and 0.7 years, with a cost per life-year saved of 63.137 to 162.417. The authors conclude that trastuzumab is not cost-effective for metastatic breast cancer. In our country, the price of trastuzumab in the drug suppliers is approximately $(argentine pesos 2005)4,900- per 440 mg vial. The annual treatment cost would be about $85,000. If we consider that, in our country, the incidence of newly diagnosed breast cancer cases is 64.7 per 100,000 people, with 34% of the patients in stage II to IV and approximately 25% overexpress HER2 and, 6 new patients every 100,000 people per year would be potential candidates to receive chemotherapy with trastuzumab.