Survival in patients with non-metastatic breast cancer treated with adjuvant trastuzumab in clinical practice.

PURPOSE: The NSABP Trial B-31 and NCCTG Trial N9831 (B-31/N9831 trials, Romond et al. in N Engl J Med 353:1673-84, 2005. doi:10.1056/NEJMoa052122; Perez et al. in J Clin Oncol 32:3744-52, 2014. doi:10.1200/JCO.2014.55.5730) established the efficacy of adjuvant trastuzumab for patients with HER2-positive early stage breast cancer. We aimed to estimate the overall survival (OS) and relapse-free survival (RFS) of HER2-positive non-metastatic breast cancer patients treated with adjuvant trastuzumab in a clinical practice setting in the United States. METHODS: Adult women initiating adjuvant trastuzumab within 1 year of breast cancer surgery were identified in the health claims database of the US Department of Defense (01/2003-12/2012). OS and RFS unadjusted rates at 4 and 6 years after the first trastuzumab treatment following the breast cancer diagnosis were estimated from Kaplan-Meier analyses. RESULTS: The study sample included 3188 women followed for a median of 3.3 years after trastuzumab initiation and treated continuously with trastuzumab for a median of 12 months. The OS rates (95 % confidence intervals) at 4 and 6 years were 90.0 % (88.6-91.2) and 87.1 (85.3-88.6), respectively. The corresponding RFS rates were 75.8 % (74.0-77.5) and 72.7 (70.7-74.7), respectively. The OS and RFS rates at 6 years reported in the B-31/N9831 trials were 89.8 and 81.4 %, respectively. CONCLUSIONS: OS rates estimated in this study were in range with those estimated in the B-31/N9831 trials, while RFS rates were lower. However, patients in the B-31/N9831 trials were younger and possibly had fewer comorbidities than patients in the current study; these differences were not adjusted for in the crude OS and RFS analyses.

Delay in initiation of adjuvant trastuzumab therapy leads to decreased overall survival and relapse-free survival in patients with HER2-positive non-metastatic breast cancer.

Trastuzumab reduces the risk of relapse in women with HER2-positive non-metastatic breast cancer, but little information exists on the timing of trastuzumab initiation. The study investigated the impact of delaying the initiation of adjuvant trastuzumab therapy for >6 months after the breast cancer diagnosis on time to relapse, overall survival (OS), and relapse-free survival (RFS) among patients with non-metastatic breast cancer. Adult women with non-metastatic breast cancer who initiated trastuzumab adjuvant therapy without receiving any neoadjuvant therapy were selected from the US Department of Defense health claims database from 01/2003 to 12/2012. Two study cohorts were defined based on the time from breast cancer diagnosis to trastuzumab initiation: >6 months and ≤6 months. The impact of delaying trastuzumab initiation on time to relapse, OS, and RFS was estimated using Cox regression models adjusted for potential confounders. Of 2749 women in the study sample, 79.9 % initiated adjuvant trastuzumab within ≤6 months of diagnosis and 20.1 % initiated adjuvant trastuzumab >6 months after diagnosis. After adjusting for confounders, patients who initiated trastuzumab >6 months after the breast cancer diagnosis had a higher risk of relapse, death, or relapse/death than those who initiated trastuzumab within ≤6 months of diagnosis (hazard ratios [95 % CIs]: 1.51 [1.22-1.87], 1.54 [1.12-2.12], and 1.43 [1.16-1.75]; respectively). The results of this population-based study suggest that delays of >6 months in the initiation of trastuzumab among HER2-positive non-metastatic breast cancer patients are associated with a higher risk of relapse and shorter OS and RFS.

Identification and cost of adverse events in metastatic breast cancer in taxane and capecitabine based regimens.

PURPOSE: We sought to compare the economic impact of treatment-related adverse events (AEs) in patients with metastatic breast cancer (mBC) using taxane- or capecitabine-based treatment regimens as either first- or second-line (FL or SL) therapy in the US. METHODS: We used healthcare claims data from the Truven Health Analytics MarketScan® Commercial Databases to conduct a retrospective cohort study comparing the economic impact of AEs amongst taxane- and capecitabine-treated mBC patients in the US. We selected women diagnosed with mBC between 2008-2010 who received a taxane or capecitabine as first- or second-line (FL or SL) chemotherapy. Costs related to hospitalization, outpatient services, emergency department visits, chemotherapy and other medications were tabulated and combined to determine total healthcare costs. The incremental monthly costs associated with the presence of AEs compared to no AEs were estimated using generalized linear models, controlling for age and Charlson Comorbidity Index. RESULTS: We identified 15,443 mBC patients meeting inclusion criteria. Adjusted total monthly costs were significantly higher in those who experienced AEs than in those without AEs in both lines of treatment (FL incremental cost: taxanes $1,142, capecitabine $1,817; SL incremental cost: taxanes $1,448, capecitabine $4,437). Total costs increased with the number of AEs and were primarily driven by increased hospitalization amongst those with AEs. CONCLUSIONS: Adverse events in taxane- or capecitabine-treated mBC patients are associated with significant increases in costs. Selecting treatment options associated with fewer AEs may reduce costs and improve outcomes in these patients.

Response to Biologic Disease-Modifying Anti-Rheumatic Drugs after Discontinuation of Anti-Tumor Necrosis Factor Alpha Agents for Rheumatoid Arthritis.

INTRODUCTION: The aim of this study was to compare the response between subsequent use of anti-tumor necrosis factor α (anti-TNF) agents and biologic disease-modifying anti-rheumatic drugs (bDMARD) with other mechanism of action (MOA) in rheumatoid arthritis (RA) patients with history of anti-TNF treatment as their first bDMARD. METHODS: A retrospective chart review was conducted at eight community-based rheumatology practices in the United States in 2012. Routine Assessment of Patient Index Data 3 (RAPID3) response was measured by comparing baseline and 6-month scores. Poor response was defined as decrease <1.8 points, follow-up score >12, or treatment discontinuation before 6 months. Percentages of patients with good and good or moderate RAPID3 response were compared for second and third biologics. Multivariate models controlled for potential confounders. RESULTS: Of 176 patients whose charts were abstracted, 122 (69.3%) received another anti-TNF agent after they discontinued their first anti-TNF. RAPID3 scores were available for 160 patients. A patient receiving a second bDMARD with another MOA had a higher good or moderate response than a patient receiving anti-TNF (53.5 vs. 30.7%, p = 0.01). In the multivariate models, treatment with another MOA was more likely to produce a good RAPID3 response [odds ratio (OR), 2.42; 95% confidence interval (CI), 1.05-5.58] or a good or moderate response (OR, 2.21; 95% CI, 1.23-3.97) than treatment with an anti-TNF. CONCLUSION: In patients who have discontinued anti-TNF agents as their first bDMARD, RAPID3 response rates are better for those receiving agents with a different MOA rather than another anti-TNF. Physicians should consider using a bDMARD with a different MOA as the next bDMARD for RA patients whose anti-TNF agent has failed.

Evaluation of erlotinib in advanced non-small cell lung cancer: impact on the budget of a U.S. health insurance plan.

BACKGROUND: Lung cancer is the most common non-skin cancer and the leading cause of cancer death among men and women in North America. More than half of all patients diagnosed with lung cancer are diagnosed with advanced disease. Most cases of lung cancer are non-small cell lung cancer (NSCLC). Erlotinib monotherapy is indicated for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least 1 prior chemotherapy regimen. OBJECTIVE: To assess the budgetary impact, from the health plan perspective, of covering erlotinib for treating patients with NSCLC stage IIIb/IV who have failed at least 1 prior chemotherapy regimen. METHODS: An Excel-based model was developed to evaluate costs for U.S. Food and Drug Administration-approved and National Comprehensive Cancer Network guideline-recommended treatment options for second- and third-line NSCLC from the perspective of a U.S. health insurer. In particular, the model compares a formulary with erlotinib and a formulary without erlotinib, including the costs of treatment, drug administration, and adverse effects. The incidence of advanced NSCLC is based on the Surveillance, Epidemiology, and End Results Cancer Registry and adverse effects related to treatment (all agents) in published results of clinical trials. Drug and treatment costs were obtained from publicly available sources in 2005. RESULTS: The base case considers a health plan of 500,000 enrollees. Assuming that erlotinib comprises 30% of second-line treatments and 90% for third-line, total costs of treating stage IIIb/IV NSCLC patients over 1 year are Dollars 382,418 with erlotinib and Dollars 380,968 without erlotinib (difference: Dollars 1,450; 90% confidence interval, -Dollars 61,376 to Dollars 29,855), less than Dollars 0.01 per member per month (PMPM) in 2005. Erlotinib direct cost is offset by reductions in standard chemotherapy-related infusion costs and adverse events. CONCLUSIONS: Based on the analysis, the inclusion of erlotinib on a formulary appears to have a relatively small impact on the annual health care budget or PMPM expenditures if it is used consistent with the product label indications.