Cost and cost-effectiveness of adjuvant trastuzumab in the real world setting: A study of the Southeast Netherlands Breast Cancer Consortium.

BACKGROUND: We assessed the real world costs and cost-effectiveness of the addition of trastuzumab in HER2 positive early breast cancer compared to chemotherapy alone in the Dutch daily practice as opposed to the results based on trial data and based on a subset of patients that were treated according to the guidelines. PATIENTS AND METHODS: In a cohort study, we included all patients with stage I-III invasive breast cancer treated with curative intent in 5 Dutch hospitals between 2005 and 2007 (n=2684).We assessed three scenarios: a real-world scenario, a trial scenario and a guideline scenario, with costs and effectiveness based on either the cohort study, the published trials or the guidelines. Incremental cost-effectiveness ratios (ICERs) and cost-effectiveness acceptability curves (CEACs) were constructed. RESULTS: Costs were €243,216 and €239,657 for trastuzumab and no trastuzumab for the real world scenario, €224,443 and €218,948 for the guideline scenario and €253,666 and €265,116 for the trial scenario. The QALYs were 0.827, 0.861, 0.993 for the real world, guideline and trial scenario. The corresponding ICERs were €4,304, €6,382 and dominance, respectively. CEACs showed that the probability that trastuzumab is cost-effective is ≥99% in each scenario. CONCLUSION: Adjuvant trastuzumab in the real world can be considered cost-effective.

Cardiotoxicity and Cardiac Monitoring During Adjuvant Trastuzumab in Daily Dutch Practice: A Study of the Southeast Netherlands Breast Cancer Consortium.

INTRODUCTION: We assessed the incidence and timing of first cardiac events, impact on trastuzumab prescription, and role of left ventricular ejection fraction (LVEF) monitoring in daily practice of trastuzumab-treated patients with human epidermal growth receptor 2 (HER2)-positive early breast cancer. METHODS: We included all patients with stage I-III breast cancer diagnosed in the early years (2005-2007) after the introduction of adjuvant trastuzumab in five hospitals in Southeast Netherlands. We studied the incidence and timing of cardiotoxicity in patients treated with adjuvant trastuzumab, using similar cardiac endpoints as in the Herceptin Adjuvant (HERA) trial. RESULTS: Of 2,684 included patients, 476 (17.7%) had a HER2-positive tumor. Of these, 269 (56.9%) were treated with adjuvant chemotherapy, and of these, 230 (85.5%) also received trastuzumab. Cardiotoxicity was observed in 29 of 230 patients (12.6%). Twenty of the 230 patients (8.7%) had symptomatic cardiotoxicity, defined as a drop in LVEF of at least 10 percentage points and to below 50%, accompanied by symptoms of congestive heart failure. Trastuzumab was definitely discontinued because of supposed cardiotoxicity in 36 patients (15.6%), of whom only 15 (6.5%) had a significant LVEF drop. Of the 36 patients who prematurely discontinued trastuzumab (including the 29 in whom cardiotoxicity was observed), 84.8% stopped in the first 6 months. No cardiac deaths were seen. CONCLUSION: In the first years after implementation of trastuzumab for treatment of early breast cancer, physicians frequently based their decision to discontinue treatment on patient symptoms apart from LVEF outcome. We suggest that focusing LVEF monitoring on the first 6 months might be more cost-effective without compromising patient safety. Nonetheless, further research is needed. IMPLICATIONS FOR PRACTICE: Knowledge of when cardiotoxicity occurs in daily practice will help shape the best follow-up method for cardiac monitoring in trastuzumab-treated patients with human epidermal growth receptor 2-positive early breast cancer. In the first years after implementation of trastuzumab for treatment of early breast cancer, physicians frequently based their decision to discontinue treatment on patient symptoms apart from left ventricular ejection fraction (LVEF) outcome. When cardiotoxicity was found in daily practice, it occurred mainly in the first 6 months after start of trastuzumab. This study suggests that focusing LVEF monitoring on the first 6 months might be more cost-effective without compromising patient safety. This insight stresses the relevance of performing real-world analyses.

Real-Life Use and Effectiveness of Adjuvant Trastuzumab in Early Breast Cancer Patients: A Study of the Southeast Netherlands Breast Cancer Consortium.

BACKGROUND: The impact of drug prescriptions in real life as opposed to strict clinical trial prescription is only rarely assessed, although it is well recognized that incorrect use may harm patients and may have a significant impact on health care resources. We investigated the use and effectiveness of adjuvant trastuzumab in daily practice compared with the effectiveness in clinical trials. METHODS: We included all patients with stage I-III invasive breast cancer, irrespective of human epidermal growth factor receptor 2 (HER2) status, diagnosed in five hospitals in the southeast of The Netherlands in 2005-2007. We aimed to assess the actual use of adjuvant trastuzumab in early HER2-positive breast and its efficacy in daily practice. RESULTS: Of 2,684 patients included, 476 (17.7%) had a HER2-positive tumor. Of these, 251 (52.7%) patients had an indication for trastuzumab treatment of which 196 (78.1%) patients actually received it. Of the 225 patients without an indication, 34 (15.1%) received trastuzumab. Five-year disease-free survival was 80.7% for (n = 230) patients treated with versus 68.2% for (n = 246) patients not treated with trastuzumab (p = .0023), and 5-year overall survival rates were 90.7% and 77.4%, respectively (p = .0002). The hazard ratio for disease recurrence was 0.63 (95% confidence interval, 0.37-1.06) for trastuzumab when adjusting for potential confounders. CONCLUSION: This study shows that in real life, patients treated with trastuzumab in early-stage HER2-positive breast cancer had a 5-year disease-free and overall survival comparable to prior randomized trials. For informative decision making, real-life data are of additional value, providing insight on outcome of patients considered ineligible for treatment.

Bridging trial and decision: a checklist to frame health technology assessments for resource allocation decisions.

OBJECTIVE: Health technology assessments (HTAs) intend to inform real-world decisions. They often draw on data from explanatory trials and hence are not always applicable to the decision problem. HTAs may therefore not meet the needs of decision makers. Our objective was to develop and apply a checklist to: 1) systematically frame HTAs in a way that they are applicable to the decision problem; and 2) assess if a decision problem can be informed by an available HTA. METHODS: We reviewed published literature to identify factors that should be considered when framing HTAs for resource allocation decisions. The checklist was finalized in collaboration with clinicians and policy makers. We applied the checklist to the economic evaluation of trastuzumab in early breast cancer. We defined a reference case and for each study, retrieved through a systematic review, we examined if each factor was explicitly considered. RESULTS: A checklist was developed with 11 factors (e.g., clinical practice, consequences, and patient use). In the case of trastuzumab, most factors were considered by the 11 retrieved economic evaluations. Two factors, being the inclusion of all relevant comparators and professional use, were considered by none of the studies. CONCLUSIONS: We developed a comprehensive checklist with 11 factors to frame HTAs and to assess the applicability of HTAs to resource allocation decisions. Economic evaluations on trastuzumab considered some of these factors, but overlooked others. The proposed checklist assists in systematically considering all factors in developing the conceptual model of an HTA, to make HTAs better reflect the decision problem.