ABSTRACT
PURPOSE: To study the treatment patterns, effectiveness and safety of zoledronic acid (ZOL) beyond 2 years of therapy, given the paucity of data on long-term treatment in daily clinical practice. METHODS: Patients with multiple myeloma (MM) or solid tumor bone metastases (STM) and at least 24 months of regular q3-4w ZOL therapy were followed prospectively for an additional 18 months beyond the 24 months required for study entry. End-points included ZOL exposure, incidence of skeletal related events (SRE), and safety. RESULTS: In all, 298 evaluable patients were enrolled. The mean continuation rate of ZOL was 90.6%. Exposure to ZOL decreased with time in all patients, but was lower (50.0% vs. 67.6%; p<0.001) and with higher discontinuation rates (incidence rate ratio [IRR]=1.95; p=0.002) in MM compared to the STM group. ZOL suppressed the rate of SREs similarly during the study as compared to before inclusion (0.12 vs. 0.13 events per person-year; p=0.7). At 18 months, 84.5% remained SRE-free. In STM patients, persistent ZOL therapy was associated with lower SRE risk (hazard ratio [HR]=0.42; p=0.01), but not in MM. Renal deterioration occurred in 3.7% and osteonecrosis of the jaw (ONJ) developed in 6.0%, with dental trauma increasing ONJ risk (HR=4.67; p=0.002). CONCLUSIONS: Beyond 2 years of therapy, treatment patterns of ZOL were heterogeneous and SRE rates were low. The safety profile of ZOL was acceptable, and interrupting ZOL in patients with solid tumors was associated with a higher risk of SREs.
Subject(s)
Bone Density Conservation Agents/administration & dosage , Bone Neoplasms/drug therapy , Bone Neoplasms/secondary , Diphosphonates/administration & dosage , Imidazoles/administration & dosage , Multiple Myeloma/drug therapy , Adult , Aged , Aged, 80 and over , Bone Density Conservation Agents/adverse effects , Diphosphonates/adverse effects , Drug Administration Schedule , Female , Humans , Imidazoles/adverse effects , Male , Middle Aged , Prospective Studies , Zoledronic AcidABSTRACT
Trastuzumab (Herceptin, Roche) is a recombinant, humanized monoclonal antibody directed against the neu-HER2 protein, since May 2002 reimbursed in Belgium for the treatment of metastatic HER2+ breast cancer and since June 2007 also in adjuvant therapy of HER2+ early stage breast cancer. The purpose of this study was to estimate the cost-effectiveness from the Belgian health care payer perspective of reimbursing trastuzumab in the Latter indication. A Markov state transition model was designed to adequately capture the natural history and course of disease for early stage breast cancer patients, and to simulate cost and disease progression over a life time perspective. The model estimates differences in outcomes for patients treated with adjuvant trastuzumab during 1 year compared to current therapy, and captures cost consequences and health benefits of trastuzumab treatment. Health benefits were expressed in terms of quality-adjusted life years gained, and future benefits were discounted at 1.5%. Costs were calculated from the perspective of the Belgian authorities' health care budget, and future costs were discounted at 3%. Where relevant, the costs per Markov state were obtained from the IMS Hospital Disease database. Additionally, an expert opinion analysis on resource use during the follow-up of treated early breast cancer patients provided the cost estimates for states with minor or without hospital costs. The incremental cost-effectiveness ratio based on a life time simulation was estimated at Euro 10,315 per quality-adjusted life year gained. It can be concluded that trastuzumab treatment of HER2+ early stage breast cancer patients is cost-effective from the perspective of the Belgian health care authorities.