Risk for stroke and myocardial infarction with abiraterone versus enzalutamide in metastatic prostate cancer patients.

BACKGROUND: Abiraterone and enzalutamide use is associated with significant cardiovascular (CV) morbidity in clinical trials, but the magnitude and clinical relevance of this association in real-world prostate cancer (PC) population remain unknown. MATERIALS AND METHODS: We retrospectively reviewed the MarketScan claims databases (1 January 2013 to 30 September 2018) to identify adults with diagnosis of metastatic PC who received treatment with androgen deprivation therapy (ADT) and novel antiandrogen agents (abiraterone or enzalutamide). The primary CV outcome measure was composite outcome of acute myocardial infarction (MI) or stroke. Secondary outcomes were individual risks of MI or stroke. We used an intention-to-treat approach to analyze the CV outcomes associated with drug exposure among patients with metastatic PC. Cox regression model was used to estimate the independent association of two drugs with CV risk after adjustment for age, baseline atrial fibrillation, and Charlson Comorbidity Index. RESULTS: A total of 6294 patients with metastatic PC who were treated with ADT and either abiraterone or enzalutamide were included in the final analysis. Of these, 4017 (63.8%) patients used abiraterone and 2217 (32.2%) patients used enzalutamide. During the study period, 255 (6.3%) primary endpoint events occurred, resulting in an incidence rate of 4.3 per 100 patient-years. In multivariable analysis, abiraterone use was associated with a 31% increased risk of MI or stroke compared to enzalutamide (hazard ratio 1.31; 95% confidence interval 1.05-1.63; P = 0.01). The incidence rate was similar in patients who switched initial therapy from abiraterone to enzalutamide or vice versa (5.0 versus 5.6 per 100 patient-years, respectively). CONCLUSIONS: To our knowledge, this is the first real-world assessment of MI and stroke among metastatic PC patients receiving novel anti-androgens. Our findings of increased MI and stroke risk with abiraterone compared with enzalutamide are consistent with data from clinical trials and suggest that enzalutamide may be preferable for prostate cancer patients at high CV risk.

Use of aspirin, other nonsteroidal anti-inflammatory drugs and acetaminophen and risk of endometrial cancer: the Epidemiology of Endometrial Cancer Consortium.

BACKGROUND: Regular use of aspirin has been associated with a reduced risk of cancer at several sites but the data for endometrial cancer are conflicting. Evidence regarding use of other analgesics is limited. PATIENTS AND METHODS: We pooled individual-level data from seven cohort and five case-control studies participating in the Epidemiology of Endometrial Cancer Consortium including 7120 women with endometrial cancer and 16 069 controls. For overall analyses, study-specific odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression and combined using random-effects meta-analysis; for stratified analyses, we used mixed-effects logistic regression with study as a random effect. RESULTS: At least weekly use of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an approximately 15% reduced risk of endometrial cancer among both overweight and obese women (OR = 0.86 [95% CI 0.76-0.98] and 0.86 [95% CI 0.76-0.97], respectively, for aspirin; 0.87 [95% CI 0.76-1.00] and 0.84 [0.74-0.96], respectively, for non-aspirin NSAIDs). There was no association among women of normal weight (body mass index < 25 kg/m2, Pheterogeneity = 0.04 for aspirin, Pheterogeneity = 0.003 for NSAIDs). Among overweight and obese women, the inverse association with aspirin was stronger for use 2-6 times/week (OR = 0.81, 95% CI 0.68-0.96) than for daily use (0.91, 0.80-1.03), possibly because a high proportion of daily users use low-dose formulations. There was no clear association with use of acetaminophen. CONCLUSION: Our pooled analysis provides further evidence that use of standard-dose aspirin or other NSAIDs may reduce risk of endometrial cancer among overweight and obese women.

Association between cytomegalovirus seropositivity and Type 2 diabetes is explained by age and other demographic characteristics: the National Health and Nutrition Examination Survey.

AIMS: To assess the association between cytomegalovirus and Type 2 diabetes among 6664 participants from the National Health and Nutrition Examination Survey. METHODS: We used existing data from adults aged 20-49 years who participated in the National Health and Nutrition Examination Survey from 1999 to 2004. Cytomegalovirus status was determined using cytomegalovirus-specific immunoglobulin G antibodies. Prevalent Type 2 diabetes was assessed through self-report or a plasma fasting glucose of ≥7 mmol/l. Logistic regression models were used to evaluate the association between Type 2 diabetes and cytomegalovirus seropositivity after adjustment for age, gender, race/ethnicity, smoking status, education, BMI and physical activity. RESULTS: In a univariate model, the crude odds of Type 2 diabetes were 47% higher in those who were cytomegalovirus-seropositive vs cytomegalovirus-seronegative. The association was attenuated and no longer significant after adjustment for age and other covariates: the odds ratio for diabetes was 1.09 (95% CI 0.71 to 1.66) for cytomegalovirus-seropositive vs -seronegative individuals. CONCLUSIONS: Our study suggests that the association between cytomegalovirus and Type 2 diabetes is explained by age and other risk factors for diabetes.

Diabetes, antidiabetic medications, and pancreatic cancer risk: an analysis from the International Pancreatic Cancer Case-Control Consortium.

BACKGROUND: Type 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications. PATIENTS AND METHODS: We analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates. RESULTS: Overall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ≥15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ≥15 years). CONCLUSION: This study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.

Cholecystectomy, gallstones, tonsillectomy, and pancreatic cancer risk: a population-based case-control study in Minnesota.

BACKGROUND: Associations between medical conditions and pancreatic cancer risk are controversial and are thus evaluated in a study conducted during 1994-1998 in Minnesota. METHODS: Cases (n=215) were ascertained from hospitals in the metropolitan area of the Twin Cities and the Mayo Clinic. Controls (n=676) were randomly selected from the general population and frequency matched to cases by age and sex. The history of medical conditions was gathered with a questionnaire during in-person interviews. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression. RESULTS: After adjustment for confounders, subjects who had cholecystectomy or gallstones experienced a significantly higher risk of pancreatic cancer than those who did not (OR (95% CI): 2.11 (1.32-3.35) for cholecystectomy and 1.97 (1.23-3.12) for gallstones), whereas opposite results were observed for tonsillectomy (0.67 (0.48-0.94)). Increased risk associated with cholecystectomy was the greatest when it occurred ≤ 2 years before the cancer diagnosis (5.93 (2.36-15.7)) but remained statistically significant when that interval was ≥ 20 years (2.27 (1.16-4.32)). CONCLUSIONS: Cholecystectomy, gallstones, and tonsillectomy were associated with an altered risk of pancreatic cancer. Our study suggests that cholecystectomy increased risk but reverse causality may partially account for high risk associated with recent cholecystectomy.