Optimal Sequence and Second-Line Systemic Treatment of Patients with RAS Wild-Type Metastatic Colorectal Cancer: A Meta-Analysis.

Although several sequential therapy options are available for treating patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), the optimal sequence of these therapies is not well established. A systematic review and meta-analysis of 13 randomized controlled trials and 4 observational studies were performed, resulting from a search of the Cochrane Library, PubMed, and Embase databases. Overall survival (OS) did not differ significantly in patients with RAS-WT failure who were administered a second-line regimen of changed chemotherapy (CT) plus anti-epidermal growth factor receptor (EGFR) versus only changed CT, changed CT plus bevacizumab versus changed CT plus anti-EGFR, or changed CT versus maintaining CT plus anti-EGFR after first-line therapy with CT, plus bevacizumab. However, OS was significantly different with a second-line regimen that included changed CT plus bevacizumab, versus only changing CT. Analysis of first-line therapy with CT plus anti-EGFR for treatment of RAS-WT mCRC indicated that second-line therapy of changed CT plus an anti-EGFR agent resulted in better outcomes than changing CT without targeted agents. The pooled data study demonstrated that the optimal choice of second-line treatment for improved OS was an altered CT regimen with retention of bevacizumab after first-line bevacizumab failure. The best sequence for first-to-second-line therapy of patients with RAS-WT mCRC was cetuximab-based therapy, followed by a bevacizumab-based regimen.

Ertapenem in the treatment of bacteremia caused by extended-spectrum beta-lactamase-producing Escherichia coli: a propensity score analysis.

OBJECTIVE: This study assessed the impact of ertapenem and other carbapenems on mortality in patients with monomicrobial extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) bacteremia. METHODS: This non-concurrent prospective study included adult patients with ESBL-EC bacteremia during a 2.5-year period at a 2200-bed teaching hospital. We used a multivariate logistic regression model and Cox's proportional hazards model including propensity score analysis to assess variables associated with 30-day mortality. RESULTS: Of 71 patients who met the study criteria, nine died within 3 days. Among the 62 remaining patients who received definitive antimicrobial therapy, 13 died within 30 days. Male gender, ICU stay, solid tumor, and primary bacteremia were independent predictors of 30-day mortality, whereas definitive antimicrobial therapy using either ertapenem or imipenem/meropenem was protective (p<0.001 and p=0.002, respectively). Adjustment by propensity score found that ertapenem appeared to exhibit more favorable outcomes, but the difference fell short of statistical significance (hazard ratio 0.02, p=0.06). Inappropriate initial therapy was not a significant predictor of mortality. CONCLUSIONS: ICU stay, but not initial choice of empirical antimicrobial therapy, was a major predictor of mortality. Using a carbapenem as definitive therapy was a protective factor for 30-day mortality. The choice of ertapenem is reasonable for less severely-ill patients who are at risk of ESBL-EC bacteremia and unlikely to have infection due to Pseudomonas aeruginosa.