The MEK inhibitor trametinib was approved in 2013 for the treatment of unresectable or metastatic melanoma with a BRAF V600E mutation, the most common pathogenic mutation in melanoma. Trametinib blocks activation of ERK1/2, inhibiting cell proliferation in melanoma. ERK1/2 also protects against multiple types of cardiac insult in mouse models. Trametinib improves survival in melanoma patients, but evidence of unanticipated cardiotoxicity is emerging. Here we describe the case of a patient with metastatic melanoma who developed acute systolic heart failure after trametinib treatment and present the results of the literature review prompted by this case. A patient with no cardiac history presented with a 6.5-mm skin lesion and was found to have metastatic BRAF V600E melanoma. Combination treatment with trametinib and the BRAF inhibitor, dabrafenib, was initiated. The patient's pre-treatment ejection fraction was 55-60%. His EF declined after 13 days and that was 40% 1 month after treatment. Two months after initiating trametinib, he developed dyspnea and fatigue. We conducted a chart review in the electronic medical record. We conducted a PubMed search using trametinib/adverse effects AND ("heart failure" OR "left ventricular dysfunction" OR hypertension OR cardiotoxicity OR mortality). We also queried the FDA Adverse Events Reporting System for reports of cardiomyopathy, ejection fraction decrease, and left ventricular dysfunction associated with trametinib between January 1, 2013, and July 20, 2017. The literature search retrieved 19 articles, including clinical trials and case reports. Early clinical experience with the MEK inhibitor trametinib suggests that its clinical efficacy may be compromised by cardiotoxicity. Further studies in humans and animals are required to determine the extent of this adverse effect, as well as its underlying mechanisms.

The approval of vismodegib represents the only targeted, prospectively studied treatment option for patients with advanced BCC. Further research assessing the utility of vismodegib in the treatment of other malignancies and the development of resistance patterns will more clearly define the role of Hedgehog inhibition in the broader scheme of oncological disorders.

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Background Patients initiating highly emetic chemotherapy (HEC) are at a 90% risk of chemotherapy-induced nausea and vomiting (CINV). Despite guideline-concordant antiemetic prescribing preventing CINV in up to 80% of patients, studies suggest that guideline-concordant antiemetic regimen use by patients initiating HEC is sub-optimal. However, these studies have been limited to single-site or single-cancer type with limited generalizability. The objective of this study was to describe antiemetic fill regimens and to assess predictors of underuse in the USA. Methods Our study population was adult patients under the age of 65 with cancer initiating intravenous HEC between 2013 and 2015 with employer-sponsored insurance in the IBM Watson/Truven MarketScan Commercial Claims database (N = 31,923). Descriptive statistics were used to explain antiemetic prescribing patterns, including antiemetic underuse. Modified Poisson regression was used to identify factors associated with antiemetic underuse. Results Among individuals initiating HEC, 49% underused guideline-concordant antiemetics. Most classified as under-using lacked an NK1 fill. While dexamethasone and 5HT3A uptake was over 80%, olanzapine use was minimal. Having lower generosity for prescription and medical benefits (paying more versus less than 20% out-of-pocket) increased the underuse risk by 3% and 4% (RR,1.03; 95% CI,1.01-1.05; P = 0.01 and RR,1.04; CI, 1.00-1.09; P = 0.03), respectively. Additionally, compared to receiving chemotherapy in the physician office setting, patients were at a 28% (RR, 1.28; 95% CI, 1.25-1.30; P < 0.0001) higher underuse risk in the outpatient hospital setting. Conclusion Antiemetic underuse is high in patients initiating HEC, potentially leading to avoidable CINVevents. We found that insurance generosity has a minimal effect on antiemetic guideline concordance in this population, suggesting discordance may be the result of site of care as well as gaps in provider knowledge or accountability.

Background High out-of-pocket costs may impact anticancer treatment uptake. The Low-Income Subsidy (LIS) program can reduce patient out-of-pocket cost for Medicare Part D–covered treatments. We examined whether the LIS increased uptake and reduced time to initiate orally administered anticancer drugs in patients with advanced non–small cell lung cancer (NSCLC). Methods Using Surveillance, Epidemiology and End Results (SEER)-Medicare data, we identified older adults (aged 65 years and older) diagnosed with advanced NSCLC from 2007 through 2013 and categorized them as full LIS, partial LIS, or non-LIS. We used propensity-score weighted (IPTW) Cox proportional hazards regression to assess the likelihood of and time to initiate Part D treatments. Part B medication uptake was our negative control because supplemental insurance reduces out-of-pocket costs for those drugs. All statistical tests were two-sided. Results Among 19 746 advanced NSCLC patients, approximately 10% initiated Part D treatments. Patients with partial or no LIS were less likely to initiate Part D treatments than were those with full subsidies (partial LIS vs full LIS HRIPTW = 0.77, 95% confidence interval = 0.62 to 0.97; non-LIS vs full LIS HRIPTW = 0.87, 95% confidence interval  = 0.79 to 0.95). Time to initiate Part D treatments was also slightly shorter among full-LIS patients (full LIS mean [SD] = 10.8 [0.04] months; partial LIS mean [SD] = 11.3 [0.08] months; and non-LIS mean [SD] = 11.1 [0.03] months, P &lt; .001). Conversely, patients with partial or no LIS had shorter time to initiation of Part B drugs. Conclusions Patients receiving the full LIS had higher orally administered anticancer treatment uptake than patients without LIS. Notably, patients with partial LIS had the lowest treatment uptake, likely because of their low incomes combined with high expected out-of-pocket spending. High out-of-pocket costs for Part D medications may be a barrier to treatment use for patients without full LIS.