Comparison of treatment patterns and economic outcomes in metastatic breast cancer patients initiated on trastuzumab versus lapatinib: a retrospective analysis.

Few studies have compared treatment patterns, healthcare resource utilization (HRU), and costs in patients with metastatic breast cancer (mBC) receiving HER2 directed therapy. This study evaluated these outcomes in patients receiving trastuzumab or lapatinib. Adult women with mBC, who were initiated on trastuzumab or lapatinib, on or after March 13, 2007, were selected from the US-based PharMetrics® Integrated Database (2000-2011). Patients were required to be continuously enrolled in their healthcare plan for ≥6 months prior to and ≥30 days following trastuzumab or lapatinib initiation. Trastuzumab or lapatinib discontinuation rates (defined as a gap ≥45 consecutive days) were compared using multivariate Cox proportional-hazards models. HRU and monthly healthcare cost differences were estimated using multivariate negative binomial regression models and generalized linear models, respectively. Among the 643 patients who met the inclusion criteria, 381 and 262 patients were included in the trastuzumab and lapatinib groups, respectively. The majority of the 262 patients receiving lapatinib previously received trastuzumab (N = 171 [65.3%]). After adjustment for potential confounders, when compared to trastuzumab patients, lapatinib patients had a higher rate of treatment discontinuation (hazard ratio [HR] = 1.57; P < 0.001), a higher rate of outpatient visits (not treatment administration related) (IRR = 1.19; P < 0.004), and a lower rate of medical visits associated with treatment administration (IRR = 0.34; P < 0.001). There were no significant differences between the two groups in total monthly healthcare costs ($11,920 vs. $11,898 for trastuzumab and lapatinib patients, respectively; P = 0.451). Findings from our study show that, irrespective of the treatment initiated at index date, disease management in patients with mBC is associated with similar and substantial healthcare costs. Any differences in specific components of healthcare costs were associated with differences in the mode of treatment administration. Approximately 50% of all costs were non-drug related, and future studies should focus on how these costs may be controlled, regardless of mode of treatment administration.

Assessing the discordance rate between local and central HER2 testing in women with locally determined HER2-negative breast cancer.

BACKGROUND: The importance of human epidermal growth factor receptor 2 (HER2) as a prognostic and predictive marker in invasive breast cancer is well established. Accurate assessment of HER2 status is essential to determine optimal treatment options. METHODS: Breast cancer tumor tissue samples from the VIRGO observational cohort tissue substudy that were locally HER2-negative were retested centrally with both US Food and Drug Administration (FDA)-approved immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays, using FDA-approved assay cutoffs; results were compared. RESULTS: Of the 552 unique patient samples centrally retested with local HER2-negative results recorded, tumor samples from 22 (4.0%) patients were determined to be HER2-positive (95% confidence interval [CI] = 2.5%-5.7%). Of these, 18 had been tested locally by only one testing methodology; 15 of 18 were HER2-positive after the central retesting, based on the testing methodology not performed locally. Compared with the 530 patients with centrally confirmed HER2-negative tumors, the 22 patients with centrally determined HER2-positive tumors were younger (median age 56.5 versus 60.0 years) and more likely to have ER/PR-negative tumors (27.3% versus 22.3%). These patients also had shorter median progression-free survival (6.4 months [95% CI = 3.8-15.9 months] versus 9.1 months [95% CI = 8.3-10.3 months]) and overall survival (25.9 months [95% CI = 13.8-not estimable] versus 27.9 months [95% CI = 25.0-32.9 months]). CONCLUSIONS: This study highlights the limitations of employing just one HER2 testing methodology in current clinical practice. It identifies a cohort of patients who did not receive potentially efficacious therapy because their tumor HER2-positivity was not determined by the test initially used. Because of inherent limitations in testing methodologies, it is inadvisable to rely on a single test to rule out potential benefit from HER2-targeted therapy.

Infused therapy and survival in older patients diagnosed with metastatic breast cancer who received trastuzumab.

We used Surveillance, Epidemiology, and End Results-Medicare data (2000-2006) to describe treatment and survival in women diagnosed with metastatic breast cancer (MBC) who received trastuzumab. There were 610 patients with a mean age of 74 years. Overall, 32% received trastuzumab alone and 47% received trastuzumab plus a taxane. In multivariate analysis, trastuzumab plus chemotherapy was associated with a lower adjusted cancer mortality rate (Hazard Ratio [HR] 0.54; 95% Confidence Interval [CI] 0.39-0.74; p < .001) than trastuzumab alone among patients who received trastuzumab as part of first-line therapy. Adding chemotherapy to first-line trastuzumab for metastatic breast cancer is associated with improved cancer survival.

Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER.

PURPOSE: registHER is a prospective, observational study of 1,023 newly diagnosed HER2-positive metastatic breast cancer (MBC) patients. EXPERIMENTAL DESIGN: Baseline characteristics of patients with and without central nervous system (CNS) metastases were compared; incidence, time to development, treatment, and survival after CNS metastases were assessed. Associations between treatment after CNS metastases and survival were evaluated. RESULTS: Of the 1,012 patients who had confirmed HER2-positive tumors, 377 (37.3%) had CNS metastases. Compared with patients with no CNS metastases, those with CNS metastases were younger and more likely to have hormone receptor-negative disease and higher disease burden. Median time to CNS progression among patients without CNS disease at initial MBC diagnosis (n = 302) was 13.3 months. Treatment with trastuzumab, chemotherapy, or surgery after CNS diagnosis was each associated with a statistically significant improvement in median overall survival (OS) following diagnosis of CNS disease (unadjusted analysis: trastuzumab vs. no trastuzumab, 17.5 vs. 3.8 months; chemotherapy vs. no chemotherapy, 16.4 vs. 3.7 months; and surgery vs. no surgery, 20.3 vs. 11.3 months). Although treatment with radiotherapy seemed to prolong median OS (13.9 vs. 8.4 months), the difference was not significant (P = 0.134). Results of multivariable proportional hazards analyses confirmed the independent significant effects of trastuzumab and chemotherapy (HR = 0.33, P < 0.001; HR = 0.64, P = 0.002, respectively). The effects of surgery and radiotherapy did not reach statistical significance (P = 0.062 and P = 0.898, respectively). CONCLUSIONS: For patients with HER2-positive MBC evaluated in registHER, the use of trastuzumab, chemotherapy, and surgery following CNS metastases were each associated with longer survival.