Summary Background Results from phase 2 and 3 trials in patients with advanced melanoma have shown significant improvements in the proportion of patients achieving an objective response and prolonged ...progression-free survival with the combination of nivolumab (an anti-PD-1 antibody) plus ipilimumab (an anti-CTLA-4 antibody) compared with ipilimumab alone. We report 2-year overall survival data from a randomised controlled trial assessing this treatment in previously untreated advanced melanoma. Methods In this multicentre, double-blind, randomised, controlled, phase 2 trial (CheckMate 069) we recruited patients from 19 specialist cancer centres in two countries (France and the USA). Eligible patients were aged 18 years or older with previously untreated, unresectable stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned 2:1 to receive an intravenous infusion of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or ipilimumab 3 mg/kg plus placebo, every 3 weeks for four doses. Subsequently, patients assigned to nivolumab plus ipilimumab received nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity, whereas patients allocated to ipilimumab alone received placebo every 2 weeks during this phase. Randomisation was done via an interactive voice response system with a permuted block schedule (block size of six) and stratification by BRAF mutation status. The study funder, patients, investigators, and study site staff were masked to treatment assignment. The primary endpoint, which has been reported previously, was the proportion of patients with BRAFV600 wild-type melanoma achieving an investigator-assessed objective response. Overall survival was an exploratory endpoint and is reported in this Article. Efficacy analyses were done on the intention-to-treat population, whereas safety was assessed in all treated patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov , number NCT01927419 , and is ongoing but no longer enrolling patients. Findings Between Sept 16, 2013, and Feb 6, 2014, we screened 179 patients and enrolled 142, randomly assigning 95 patients to nivolumab plus ipilimumab and 47 to ipilimumab alone. In each treatment group, one patient no longer met the study criteria following randomisation and thus did not receive study drug. At a median follow-up of 24·5 months (IQR 9·1–25·7), 2-year overall survival was 63·8% (95% CI 53·3–72·6) for those assigned to nivolumab plus ipilimumab and 53·6% (95% CI 38·1–66·8) for those assigned to ipilimumab alone; median overall survival had not been reached in either group (hazard ratio 0·74, 95% CI 0·43–1·26; p=0·26). Treatment-related grade 3–4 adverse events were reported in 51 (54%) of 94 patients who received nivolumab plus ipilimumab compared with nine (20%) of 46 patients who received ipilimumab alone. The most common treatment-related grade 3–4 adverse events were colitis (12 13% of 94 patients) and increased alanine aminotransferase (ten 11%) in the combination group and diarrhoea (five 11% of 46 patients) and hypophysitis (two 4%) in the ipilimumab alone group. Serious grade 3–4 treatment-related adverse events were reported in 34 (36%) of 94 patients who received nivolumab plus ipilimumab (including colitis in ten 11% of 94 patients, and diarrhoea in five 5%) compared with four (9%) of 46 patients who received ipilimumab alone (including diarrhoea in two 4% of 46 patients, colitis in one 2%, and hypophysitis in one 2%). No new types of treatment-related adverse events or treatment-related deaths occurred in this updated analysis. Interpretation Although follow-up of the patients in this study is ongoing, the results of this analysis suggest that the combination of first-line nivolumab plus ipilimumab might lead to improved outcomes compared with first-line ipilimumab alone in patients with advanced melanoma. The results suggest encouraging survival outcomes with immunotherapy in this population of patients. Funding Bristol-Myers Squibb.
Background Shoulder arthroplasty is an effective procedure for managing patients with shoulder pain secondary to end-stage arthritis. Insurance status has been shown to be a predictor of patient ...morbidity and mortality. The current study evaluated the effect of patient insurance status on perioperative outcomes after shoulder replacement surgery. Methods Data between 2004 and 2011 were obtained from the Nationwide Inpatient Sample. Analysis included patients undergoing shoulder arthroplasty (partial, total, and reverse) procedures determined by International Classification of Disease, 9th Revision procedure codes. The primary outcome was medical and surgical complications occurring during the same hospitalization, with secondary analyses of mortality and hospital charges. Additional analyses using the coarsened exact matching algorithm were performed to assess the influence of insurance type in predicting outcomes. Results A data inquiry identified 103,290 shoulder replacement patients (68,578 Medicare, 27,159 private insurance, 3544 Medicaid/uninsured, 4009 other). The overall complication rate was 17.2% (n = 17,810) and the mortality rate was 0.20% (n = 208). Medicare and Medicaid/uninsured patients had a significantly higher rate of medical, surgical, and overall complications compared with private insurance using the controlled match data. Multivariate regression analysis found that having private insurance was associated with fewer overall medical complications. Conclusion Private insurance payer status is associated with a lower risk of perioperative medical and surgical complications compared with an age- and sex-matched Medicare and Medicaid/uninsured payer status. Mortality was not statistically associated with payer status. Primary insurance payer status should be considered as an independent risk factor during preoperative risk stratification for shoulder arthroplasty procedures.
Abstract Background The direct anterior approach (DAA) for total hip arthroplasty (THA) has rapidly become popular, but there is little consensus regarding the risks and benefits of this approach in ...comparison with a modern posterior approach (PA). Methods A total of 2147 patients who underwent DAA THA were propensity score matched with patients undergoing PA THA on the basis of age, gender, body mass index, and American Society of Anesthesia classification using data from a state joint replacement registry. Mean age of the matched cohort was 64.8 years, mean body mass index was 29.1 kg/m2 , and 53% were female. Multilevel logistic regression models using generalized estimating equations to control for grouping at the hospital level were used to identify differences in various outcomes. Results There was no difference in the dislocation rate between patients undergoing DAA (0.84%) and PA (0.79%) THA. Trends indicating a slightly longer length of stay with the PA and a slightly greater risk of fracture, increased blood loss, and hematoma with the DAA are consistent with previous studies. Conclusion On the basis of short-term outcome and complication data, neither approach has a compelling advantage over each other, including no difference in the dislocation risk.
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