Bin Riaz, Irbaz

Background Thromboprophylaxis is routinely used with lenalidomide‐based regimens in multiple myeloma because of a substantial risk of venous thromboembolism (VTE). However, little is known about the incidence of VTE with contemporary lenalidomide‐based regimens. The objective of the current study was to estimate the incidence of VTE despite thromboprophylaxis with currently used lenalidomide‐based regimens in patients with myeloma. Methods The Ovid MEDLINE, Embase, and Cochrane databases were queried from study inception to January 2019 for keywords to cover the following concepts: “lenalidomide,” “venous thromboembolism,” and “multiple myeloma.” Phase 1, 2, and 3 clinical trials evaluating lenalidomide‐based regimens with thromboprophylaxis were included. The pooled incidence rate of VTE was estimated using a random‐effects model. Results The search generated 1372 citations, with 51 clinical trials and 9069 patients included for analysis. The most common thromboprophylaxis agents were aspirin, low‐molecular‐weight heparin or warfarin, administered either per risk‐stratification or at investigators' discretion. The pooled incidence of VTE in trials of patients who had newly diagnosed and relapsed/refractory myeloma was 6.2% (95% CI, 5.4%‐7.1%) over median treatment durations ranging from 2 to 34 cycles, which translated into 1.2 VTE events per 100 patient‐cycles (95% CI, 0.9‐1.7 VTE events per 100 patient‐cycles). Among contemporary regimens, the risk of VTE was low with combined lenalidomide and low‐dose dexamethasone (0.2 [95% CI, 0.1‐0.6] events/100 patient‐cycles) and lenalidomide maintenance (0.0 [95% CI, 0.0‐0.7] events per 100 patient‐cycles). VTE risk was higher with combined lenalidomide and low‐dose dexamethasone plus proteasome inhibitors (1.3 [95% CI, 0.7‐2.3] events per 100 patient‐cycles). Conclusions Despite adequate thromboprophylaxis, lenalidomide‐based regimens have a substantial risk of VTE in controlled clinical trial settings. Further studies are needed on new thromboprophylaxis strategies with regimens that have a high VTE risk.

Background Male breast cancer (MBC) is a rare disease for which there is limited understanding of treatment patterns and prognostic factors. Methods Men with TNM stage I to stage III breast cancer diagnosed between 2004 and 2014 in the National Cancer Data Base were included. Trends in treatment modalities were described using the average annual percentage change (AAPC) and estimated using Joinpoint software for the analysis of trends. Kaplan‐Meier curves and the multivariate Cox proportional hazards regression model were used to compare survival between subgroups and to identify prognostic factors. Results A total of 10,873 MBC cases were included, with a median age at diagnosis of 64 years. Breast‐conserving surgery was performed in 24% of patients, and 70% of patients undergoing breast conservation received radiotherapy. Approximately 44% of patients received chemotherapy, and 62% of patients with estrogen receptor–positive disease received endocrine therapy. Oncotype DX was ordered in 35% of patients with lymph node–negative, estrogen receptor–positive/human epidermal growth factor receptor 2 (HER2)‐negative tumors. During the study period, there was a significant increase in the rates of total mastectomy, contralateral prophylactic mastectomy, radiotherapy after breast conservation, ordering of Oncotype DX, and the use of endocrine therapy ( P < .05). On multivariate analysis, factors found to be associated with worse overall survival were older age, black race, higher Charlson Comorbidity Index, high tumor grade and stage of disease, and undergoing total mastectomy. Residing in a higher income area; having progesterone receptor–positive tumors; and receipt of chemotherapy, radiotherapy, and endocrine therapy were associated with better overall survival. Conclusions Despite the lack of prospective randomized trials in patients with MBC, the results of the current study demonstrated that the treatment of this disease has evolved over the years. These findings further the understanding of the modern treatment and prognosis of MBC, and identify several areas for further research.

Background The comparative effects of statins, ezetimibe with or without statins and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remain unassessed. Design Bayesian network meta-analysis was conducted to compare treatment groups. Methods Thirty-nine randomized controlled trials were selected using MEDLINE, EMBASE, and CENTRAL (inception – September 2017). Results In network meta-analysis of 189,116 patients, PCSK9 inhibitors were ranked as the best treatment for prevention of major adverse cardiovascular events (Surface Under Cumulative Ranking Curve (SUCRA), 85%), myocardial infarction (SUCRA, 84%) and stroke (SUCRA, 80%). PCSK9 inhibitors reduced the risk of major adverse cardiovascular events compared with ezetimibe + statin (odds ratio (OR): 0.72; 95% credible interval (CrI), 0.55–0.95; Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria: moderate), statin (OR: 0.78; 95% CrI: 0.62–0.97; GRADE: moderate) and placebo (OR: 0.63; 95% CrI: 0.49–0.79; GRADE: high). The PCSK9 inhibitors were consistently superior to groups for major adverse cardiovascular event reduction in secondary prevention trials (SUCRA, 95%). Statins had the highest probability of having lowest rates of all-cause mortality (SUCRA, 82%) and cardiovascular mortality (SUCRA, 84%). Compared with placebo, statins reduced the risk of all-cause mortality (OR: 0.88; 95% CrI: 0.83–0.94; GRADE: moderate) and cardiovascular mortality (OR: 0.84; 95% CrI: 0.77–0.90; GRADE: high). For cardiovascular mortality, PCSK9 inhibitors were ranked as the second best treatment (SUCRA, 78%) followed by ezetimibe + statin (SUCRA, 50%). Conclusion PCSK9 inhibitors were ranked as the most effective treatment for reducing major adverse cardiovascular events, myocardial infarction and stroke, without having major safety concerns. Statins were ranked as the most effective therapy for reducing mortality.