Outcome and Biomarker Analysis from a Multicenter Phase 2 Study of Ipilimumab in Combination with Carboplatin and Etoposide as First-Line Therapy for Extensive-Stage SCLC.

OBJECTIVES: Our aim was to evaluate the safety and efficacy of ipilimumab combined with standard first-line chemotherapy for patients with extensive-stage SCLC. METHODS: Patients with chemotherapy-naive extensive-stage SCLC were treated with carboplatin and etoposide for up to six cycles. Ipilimumab, 10 mg/kg, was given on day 1 of cycles 3 to 6 and every 12 weeks. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0, and immune-related response criteria. The primary end point was 1-year progression-free survival (PFS) according to RECIST. Secondary end points included PFS according to immune-related PFS and overall survival. Autoantibody serum levels were evaluated and correlated with clinical outcomes. RESULTS: A total of 42 patients were enrolled between September 2011 and April 2014; 39 were evaluable for safety and 38 for efficacy. Six of 38 patients (15.8% [95% confidence interval (CI): 7.4-30.4]) were alive and progression-free at 1-year by RECIST. Median PFS was 6.9 months (95% CI: 5.5-7.9). Median immune-related PFS was 7.3 months (95% CI: 5.5-8.8). Median overall survival was 17.0 months (95% CI: 7.9-24.3). Of the patients evaluable for response, 21 of 29 (72.4%) achieved an objective response by RECIST and 28 of 33 (84.8%) achieved an objective response by the immune-related response criteria. All patients experienced at least one adverse event; at least one grade 3 or higher toxicity developed in 35 of 39 patients (89.7%); in 27 patients (69.2%) this was related to ipilimumab. Five deaths were reported to be related to ipilimumab. Positivity of an autoimmune profile at baseline was associated with improved outcomes and severe neurological toxicity. CONCLUSIONS: Ipilimumab in combination with carboplatin and etoposide might benefit a subgroup of patients with advanced SCLC. Autoantibody analysis correlates with treatment benefit and toxicity and warrants further investigation.

The influence of client's ethnicity on psychotropic medication management in community mental health services.

OBJECTIVES: The aim of this study was to investigate whether people born in non-English-speaking countries differed from clients born in Australia on quality of medication management, measured by mean neuroleptic dose, method of administration, use of atypical antipsychotics and perceived compliance with medication, and to investigate the influence of matching the client with a case manager from the same ethnic background on these measures. METHOD: Information about medication and perceived compliance was provided for 168 clients of five community mental health services in Melbourne. Chlorpromazine equivalent doses (CPZe) were calculated, and average dose, route of administration, percentage receiving atypical antipsychotics and perceived compliance with medication were analysed by country of birth and preferred language. Each analysis was repeated for clients matched to a case manager from the same ethno-linguistic background compared to those with 'unmatched' case managers. RESULTS: While non-English-speaking background (NESB) clients generally did not receive different dose sizes, those born in Vietnam had a lower mean dose. People born in a non-English-speaking country tended to be more likely than the Australian born to receive a depot injection, although this was not quite statistically significant. Twenty-seven percent of clients received an atypical neuroleptic; age was a significant factor, with older clients less likely to receive an atypical. There was no difference in receipt of atypicals or perceived compliance by country of birth, language or gender. Matching for a case manager of the same background had no effect except for route of administration, with matched clients less likely to receive depot medication than unmatched. CONCLUSIONS: Generally, the ethnic background of clients had little influence on the quality of medication management they received from community mental health services.