U.S. Food and Drug Administration approval summary: Erlotinib for the first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) substitution mutations.

On May 14, 2013, the U.S. Food and Drug Administration approved erlotinib (Tarceva, Astellas Pharma Inc., Northbrook, IL, http://www.us.astellas.com/) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. This indication for erlotinib was approved concurrently with the cobas EGFR Mutation Test (Roche Molecular Systems, Inc., Basel, Switzerland, http://www.molecular.roche.com), a companion diagnostic test for patient selection. The approval was based on clinically important improvements in progression-free survival (PFS) and objective response rate (ORR) and an acceptable toxicity profile demonstrated in a multicenter, open label trial enrolling 174 patients with metastatic NSCLC whose tumors had EGFR mutations as determined by a laboratory-developed test. Patients were randomized (1:1) to receive erlotinib (150 mg/day) or platinum-based doublet chemotherapy. The primary endpoint was investigator-assessed PFS. Secondary endpoints included overall survival (OS) and ORR. Superior PFS (hazard ratio [HR] 0.34; 95% confidence interval [CI]: 0.23, 0.49; p < .001) and ORR (65% vs. 16%) were observed in the erlotinib arm. Median PFS was 10.4 months and 5.2 months in the erlotinib and chemotherapy arms, respectively. There was no difference in OS (HR 0.93; 95% CI: 0.64, 1.35) with median OS of 22.9 months and 19.5 months in the erlotinib and chemotherapy arms, respectively. The most frequent (≥30%) adverse reactions in the erlotinib-treated patients were rash, diarrhea, asthenia, cough, dyspnea, and decreased appetite. The most frequent (≥5%) grade 3 and 4 adverse reactions were rash and diarrhea.

Challenges and opportunities in healthcare volunteer management: insights from volunteer administrators.

Volunteer administrators from 105 hospitals in five states in the northeast and southern United States provided open-ended survey responses about what they perceived to be the most pressing challenges and opportunities facing healthcare volunteer management. Taken together, these 105 hospitals used a total of 39,008 volunteers and 5.3 million volunteer hours during a 12-month period between 2010 and 2011. A qualitative content analysis of administrator responses suggests that primary challenges include volunteer recruitment and retention, administrative issues, and operational difficulties brought about by the current economic crisis. Key opportunities include more explicitly linking the volunteer function to hospital outcomes and community impact, expanding volunteer recruitment pools and roles and jobs, and developing organizational support for volunteers and making the volunteer management function more efficient and effective.

FDA approval: ceritinib for the treatment of metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer.

On April 29, 2014, the FDA granted accelerated approval to ceritinib (ZYKADIA; Novartis Pharmaceuticals Corporation), a breakthrough therapy-designated drug, for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. The approval was based on a single-arm multicenter trial enrolling 163 patients with metastatic ALK-positive NSCLC who had disease progression on (91%) or intolerance to crizotinib. Patients received ceritinib at a starting dose of 750 mg orally once daily. The objective response rate (ORR) by a blinded independent review committee was 44% (95% CI, 36-52), and the median duration of response (DOR) was 7.1 months. The ORR by investigator assessment was similar. Safety was evaluated in 255 patients. The most common adverse reactions and laboratory abnormalities included diarrhea (86%), nausea (80%), increased alanine transaminase (80%), increased aspartate transaminase (75%), vomiting (60%), increased glucose (49%), and increased lipase (28%). Although 74% of patients required at least one dose reduction or interruption due to adverse reactions, the discontinuation rate due to adverse reactions was low (10%). With this safety profile, the benefit-risk analysis was considered favorable because of the clinically meaningful ORR and DOR.

Success and shortcomings of a clinical care pathway in the management of acute nonvariceal upper gastrointestinal bleeding.

OBJECTIVES: Acute nonvariceal upper gastrointestinal (GI) bleeding is the most common medical emergency encountered by gastroenterologists resulting in high patient morbidity and cost. We sought to establish if a GI bleeding clinical care pathway could improve the quality and cost effectiveness of inpatient medical care. METHODS: A disease management program for acute upper GI bleeding was established. Length of stay, time to endoscopy, utilization of potentially unnecessary radiological tests, acid suppression, and cost of care were compared between patients pre- and postinitiation of GI bleeding pathway guidelines. RESULTS: The instituted GI bleeding management program significantly reduced the use of intravenous H2-blockade from 65.3% to 47.7% (p = 0.002). The use of radiological tests, time to endoscopy, and length of hospital of stay were unchanged. There was a trend toward a reduction in total cost and variable direct cost per patient admitted with acute upper GI bleeding, from $5,381 to $4,627 and from $2,269 to $1,952, respectively. CONCLUSION: A clinical care pathway may affect the management of acute upper GI bleeding and reduce costs. However, there are significant limitations and barriers to the overall effectiveness of such a pathway in actual clinical practice.