Philip Galebach

The natural history of brain volume loss among patients with multiple sclerosis: A systematic literature review and meta-analysis

BACKGROUND Multiple sclerosis has been associated with progressive brain volume loss. OBJECTIVE We aimed to systematically summarize reported rates of brain volume loss in multiple sclerosis and explore associations between brain volume loss and markers of disease severity. METHODS A systematic literature search (2003-2013) was conducted to identify studies with ≥12months of follow-up, reported brain volume measurement algorithms, and changes in brain volume. Meta-analysis random-effects models were applied. Associations between brain volume change, changes in lesion volume and disease duration were examined in pre-specified meta-regression models. RESULTS We identified 38 studies. For the meta-analysis, 12 studies that reported annualized percentage brain volume change (PBVC), specified first-generation disease-modifying treatments (e.g., interferon-beta or glatiramer acetate) and used Structural Image Evaluation of Normalized Atrophy algorithm were analyzed. The annualized PBVC ranged from -1.34% to -0.46% per year. The pooled PBVC was -0.69% (95% CI=-0.87% to -0.50%) in study arms receiving first-generation disease-modifying treatments (N=6 studies) and -0.71% (95% CI=-0.81% to -0.61%) in untreated study arms (N=6 studies). CONCLUSIONS In this study, the average multiple sclerosis patient receiving first-generation disease-modifying treatment or no disease-modifying treatment lost approximately 0.7% of brain volume/year, well above rates associated with normal aging (0.1%-0.3% of brain volume/year).

Treatment patterns and outcomes in BRAF V600E-mutant melanoma patients with brain metastases receiving vemurafenib in the real-world setting

Brain metastases are a common and serious complication among patients with metastatic melanoma. The selective BRAF inhibitor vemurafenib has demonstrated clinical efficacy in patients with BRAF V600E‐mutant melanoma brain metastases (MBM). We examined the real‐world application and clinical outcomes of vemurafenib in this patient population. Demographic, treatment patterns, response, and survival data were collected from medical charts. Clinical data on 283 patients with active BRAF V600E‐mutant MBM treated with vemurafenib were provided by 70 US oncologists. Mean age was 57.2 years, 60.8% were male, 67.5% had ECOG performance status of 0–1, and 43.1% used corticosteroids at vemurafenib initiation. Median follow‐up was 5.7 months. Following vemurafenib initiation, 48.1% of patients experienced intracranial response and 45.6% experienced extracranial response. The Kaplan–Meier estimate for overall survival was 59% at 12 months. Multivariate analyses showed associations between intracranial response and both corticosteroid use and vemurafenib as initial therapy after MBM diagnosis. Larger size (5–10 mm vs. <5 mm) and number of brain metastases (≥5 vs. <2) and progressive extracranial disease at treatment initiation were associated with decreased intracranial response and increased risk of disease progression. Multiple extracranial sites (2 vs. <2) and the absence of local treatments were also associated with increased risk of progression. Increased risk of death was associated with ≥2 extracranial disease sites, progressive extracranial disease, and ≥5 brain metastases. Subgroups of MBM patients may derive more benefit with vemurafenib, warranting prospective investigation.

Treatment, overall survival, and costs in patients with ALK-positive non-small-cell lung cancer after crizotinib monotherapy

Abstract Background: Limited post-crizotinib treatment options for ALK-positive non-small cell lung cancer (NSCLC) might lead to poor survival and high economic burden. Objective: To evaluate real-world treatment patterns, overall survival (OS), and costs following crizotinib discontinuation. Methods: This study used chart review and claims data. First, 27 participating US oncologists reviewed medical records of ALK-positive NSCLC patients who discontinued crizotinib monotherapy and reported patient demographic and clinical information, including post-crizotinib treatment and mortality. OS was estimated using Kaplan–Meier analyses. Second, three large administrative US claims databases were pooled. NSCLC patients were selected if they discontinued crizotinib monotherapy. Post-crizotinib costs were analyzed separately for patients who did or did not discontinue antineoplastic treatment after crizotinib monotherapy. All data were collected prior to ceritinib approval for this patient population. Results: A total of 119 ALK-positive NSCLC patients discontinued crizotinib monotherapy. Upon discontinuation, 42% had no additional antineoplastic treatment and 13% received radiation therapy only. The median OS post-crizotinib was 61 days; patients with brain metastases had shorter OS than those who did not (44 vs. 69 days, P = 0.018), and patients without further antineoplastic treatment had shorter OS than those who did (17 vs. 180 days, P < 0.001). From claims data, 305 ALK-positive NSCLC patients discontinued crizotinib monotherapy. After discontinuation, 72% had no additional antineoplastic treatment. Among patients who continued antineoplastic treatment, monthly healthcare costs averaged

Characteristics, treatment patterns, and survival among ALK+ non-small cell lung cancer (NSCLC) patients treated with crizotinib: A chart review study

22,160, driven by pharmacy (

Healthcare resource utilization and work loss in dermatomyositis and polymyositis patients in a privately-insured US population

9202), inpatient (

The burden of hepatorenal syndrome among commercially insured and Medicare patients in the United States

6419), and outpatient radiotherapy (

Assessing utility values for treatment-related health states of acute myeloid leukemia in the United States

2888) and imaging (

Characteristics and outcomes of ALK+ non‐small cell lung cancer patients in Korea

1179) costs. Among patients who discontinued any antineoplastic treatment, monthly healthcare costs averaged

PS01.70: Ceritinib Dosing Patterns and Outcomes of Patients with ALK+ NSCLC in a Real-World Practice in the United States: Topic: Medical Oncology

3423, mostly driven by inpatient costs (

1104PPREDICTORS OF TREATMENT (TX) RESPONSE AND PROGRESSION IN BRAF V600E METASTATIC MELANOMA (MM) PATIENTS (PTS) WITH BRAIN METASTASES (BM) RECEIVING VEMURAFENIB (VEM) IN A REAL-WORLD SETTING

2074). Conclusions: After crizotinib monotherapy, most patients either received radiotherapy only or discontinued antineoplastic treatment altogether. OS after discontinuing crizotinib was poor and shorter among those with brain metastases than without, and among those without subsequent antineoplastic treatment than with. Patients who continued antineoplastic treatment incurred substantial healthcare costs.