Real-world Safety of Bevacizumab with First-line Combination Chemotherapy in Patients with Metastatic Colorectal Cancer: Population-based Retrospective Cohort Studies in Three Canadian Provinces.

AIMS: To examine the real-world safety of adding bevacizumab to first-line irinotecan-based chemotherapy for patients with metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: Patients diagnosed with CRC in three Canadian provinces (Ontario, Saskatchewan and British Columbia) who received publicly funded bevacizumab and/or irinotecan from 2000 to 2016 were identified from cancer registries. Propensity score 1:1 matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to contemporaneous and historical controls, adjusting for baseline demographic and clinical characteristics. Safety end points evaluated during first-line treatment plus 30 days included mortality within 30 days and all-cause-, chemotherapy- and bevacizumab-related hospitalisations. Chemotherapy- and bevacizumab-related visits were defined as hospitalisations for specific conditions commonly associated with chemotherapy (e.g. infections) or bevacizumab (e.g. arteriovenous thromboembolism) using most responsible diagnosis codes. In PSM and IPTW-weighted cohorts, we assessed event frequencies using odds ratios from logistic regressions and event rate ratios using negative binomial regression models. The results from each province and comparison were pooled using random-effects meta-analysis. RESULTS: We identified 16 250 mCRC patients who received first-line irinotecan-based treatment. In PSM cohorts, bevacizumab was associated with fewer deaths within 30 days of treatment compared with contemporaneous (pooled odds ratio = 0.62; 95% confidence interval 0.50-0.75) and historical controls (pooled odds ratio = 0.73; 95% confidence interval 0.58-0.93). Hospitalisations were more frequent among patients treated with bevacizumab compared with historical controls but similar to contemporaneous controls. As patients receiving bevacizumab were exposed to a longer average treatment duration, across their full treatment duration, patients receiving bevacizumab had significantly lower rates of hospitalisations (contemporaneous pooled rate ratio = 0.56; 95% confidence interval 0.47-0.67; historical pooled rate ratio = 0.73; 95% confidence interval 0.56-0.95). Similar trends were observed for chemotherapy- and bevacizumab-related hospitalisations and in IPTW-weighted cohorts. DISCUSSION: We did not observe any increase in rates of hospitalisation or death within 30 days of treatment among mCRC patients treated with bevacizumab plus chemotherapy versus chemotherapy alone; these findings should be interpreted with caution due to the risk of residual confounding.

Cost-utility analysis of 21-gene assay for node-positive early breast cancer.

Background: For women with lymph node (ln)-positive, estrogen receptor-positive, and her2 (human epidermal growth factor receptor 2)-negative breast cancer (bca), current guidelines recommend treatment with both hormonal therapy and chemotherapy. The 21-gene Recurrence Score (rs) assay might be helpful in selecting patients with bca who can be spared chemotherapy when they have 1-3 positive lns and a lower risk of recurrence. In the present study, we performed a cost-utility analysis comparing use of the 21-gene rs assay with current practice from the perspective of a Canadian health care payer. Methods: A Markov model was developed to determine costs and quality-adjusted life-years (qalys) over a patient's lifetime. Patient outcomes in both study groups were examined based on published clinical trials. Costs were derived primarily from published Canadian sources. Costs and outcomes were discounted at 1.5% annually, and costs are reported in 2016 Canadian dollars. A probabilistic analysis was used, and the model parameters were varied in a sensitivity analysis. Results: The results indicate that use of the 21-gene rs assay was less costly ($432 less) and more effective (0.22 qalys) than current practice. The probabilistic analysis revealed that 70% of the 10,000 simulated incremental cost-effectiveness ratios were in the southeast quadrant. The results were sensitive to the probability of a low rs and to the probability of receiving chemotherapy in the low-risk rs category and in current practice. Conclusions: Use of the 21-gene rs assay could be a cost-effective strategy for Ontario patients with estrogen receptor-positive, her2-negative early bca and 1-3 positive lns.

Are patient education materials about cancer screening more effective when co-created with patients? A qualitative interview study and randomized controlled trial.

Background: Patient education materials (pems) are frequently used to help patients make cancer screening decisions. However, because pems are typically developed by experts, they might inadequately address patient barriers to screening. We co-created, with patients, a prostate cancer (pca) screening pem, and we compared how the co-created pem and a pem developed by experts affected decisional conflict and screening intention in patients. Methods: We identified and used patient barriers to pca screening to co-create a pca screening pem with patients, clinicians, and researchers. We then conducted a parallel-group randomized controlled trial with men 40 years of age and older in Ontario to compare decisional conflict and intention about pca screening after those men had viewed the co-created pem (intervention) or an expert-created pem (control). Participants were randomized using dynamic block randomization, and the study team was blinded to the allocation. Results: Of 287 participants randomized to exposure to the co-created pem, 230 were analyzed, and of 287 randomized to exposure to the expert-created pem, 223 were analyzed. After pem exposure, intervention and control participants did not differ significantly in Decisional Conflict Scale scores [mean difference: 0.37 ± 1.23; 95% confidence interval (ci): -2.05 to 2.79]; in sure (Sure of myself, Understand information, Risk-benefit ratio, or Encouragement) scores (odds ratio: 0.75; 95% ci: 0.52 to 1.08); or in screening intention (mean difference: 0.09 ± 0.08; 95% ci: -0.06 to 0.24]). Conclusions: The effectiveness of the co-created pem did not differ from that of the pem developed by experts. Thus, pem developers should choose the method that best fits their goals and resources.