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Background:The randomised phase III TURANDOT trial compared first-line bevacizumab-paclitaxel (BEV-PAC) vs bevacizumab-capecitabine (BEV-CAP) in HER2-negative locally recurrent/metastatic breast cancer (LR/mBC). The interim analysis revealed no difference in overall survival (OS; primary end point) between treatment arms; however, progression-free survival (PFS) and objective response rate were significantly superior with BEV-PAC. We sought to identify patient populations that may be most appropriately treated with one or other regimen.Methods:Patients with HER2-negative LR/mBC who had received no prior chemotherapy for advanced disease were randomised to either BEV-PAC (bevacizumab 10 mg kg−1 days 1 and 15 plus paclitaxel 90 mg m−2 days 1, 8 and 15 q4w) or BEV-CAP (bevacizumab 15 mg kg−1 day 1 plus capecitabine 1000 mg m−2 bid days 1-14 q3w). The study population was categorised into three cohorts: triple-negative breast cancer (TNBC), high-risk hormone receptor-positive (HR+) and low-risk HR+. High- and low-risk HR+ were defined, respectively, as having ⩾2 vs ⩽1 of the following four risk factors: disease-free interval ⩽24 months; visceral metastases; prior (neo)adjuvant anthracycline and/or taxane; and metastases in ⩾3 organs.Results:The treatment effect on OS differed between cohorts. Non-significant OS trends favoured BEV-PAC in the TNBC cohort and BEV-CAP in the low-risk HR+ cohort. In all three cohorts, there was a non-significant PFS trend favouring BEV-PAC. Grade ⩾3 adverse events were consistently less common with BEV-CAP.Conclusions:A simple risk factor index may help in selecting bevacizumab-containing regimens, balancing outcome, safety profile and patient preference. Final OS results are expected in 2015 (ClinicalTrials.gov NCT00600340). [ABSTRACT FROM AUTHOR]

Background: The randomised phase III TANIA trial demonstrated that continuing bevacizumab with second-line chemotherapy for locally recurrent/metastatic breast cancer (LR/mBC) after progression on first-line bevacizumabcontaining therapy significantly improved progression-free survival (PFS) compared with chemotherapy alone [hazard ratio (HR) = 0.75, 95% confidence interval (CI) 0.61-0.93].We report final results from the TANIA trial, including overall survival (OS) and health-related quality of life (HRQoL). Patients and methods: Patients with HER2-negative LR/mBC that had progressed on or after first-line bevacizumab plus chemotherapy were randomised to receive standard second-line chemotherapy either alone or with bevacizumab. At second progression, patients initially randomised to bevacizumab continued bevacizumab with their third-line chemotherapy, but those randomised to chemotherapy alone were not allowed to cross over to receive third-line bevacizumab. The primary end point was second-line PFS; secondary end points included third-line PFS, combined second- and thirdline PFS, OS, HRQoL and safety. Results: Of the 494 patients randomised, 483 received second-line therapy; 234 patients (47% of the randomised population) continued to third-line study treatment. The median duration of follow-up at the final analysis was 32.1 months in the chemotherapy-alone arm and 30.9 months in the bevacizumab plus chemotherapy arm. There was no statistically significant difference between treatment arms in third-line PFS (HR = 0.79, 95% CI 0.59-1.06), combined second- and third-line PFS (HR = 0.85, 95% CI 0.68-1.05) or OS (HR = 0.96, 95% CI 0.76-1.21). Third-line safety results showed increased incidences of proteinuria and hypertension with bevacizumab, consistent with safety results for the second-line treatment phase. No differences in HRQoL were detected. Conclusions: In this trial, continuing bevacizumab beyond first and second progression of LR/mBC improved secondline PFS, but no improvement in longer term efficacy was observed. The second-line PFS benefit appears to be achieved without detrimentally affecting quality of life. [ABSTRACT FROM AUTHOR]

Background. We earlier reported patient-related factors influencing the delay in first medical advice for signs of BC in selected countries (J Clin Oncol 2012;30[15S]:578s). The present analysis, which includes additional countries, addresses the factors influencing time from first symptoms of BC to initiation of treatment (Total Delay Time; TDT). Methods. A total of 6,588 female BC patients from 11 countries were surveyed using a uniform questionnaire translated into local languages. TDT was determined using 8 individual scales, including one pertaining to patient delay and 7 related to subsequent steps in a typical diagnostic process. Regression models were constructed using 18 variables concerning diverse contextual and personal patient characteristics. Due to expected differences in the relevant sets of predictors, time between first symptoms and first medical visit (Patient Delay Time; PDT) and time between first medical visit and start of therapy (System Delay Time; SDT) were modeled separately, with multilevel regression. Results. Mean TDT varied in individual countries from 11.5 to 29.4 weeks (grand mean of 14.3 weeks; see table), with 43% of cases with a delay of >12 weeks. Multilevel regression equation indicated that factors significantly correlated with longer PDT were distrust in the medical system and ignoring disease. Patients with fear of the disease, stronger self-examination habits, at least secondary education, being employed, reporting more support from friends and family, and living in cities of >100,000 inhabitants had shorter PDT. Predictors of shorter SDT included being diagnosed by an oncologist vs. other physician, having at least secondary education, being older than 60 years, having a history of cancer in female relatives and having breast lump vs. other BC symptoms. Indicators of longer SDT were PDT >4 weeks, more than one BC symptom detected by patient, distrust in the medical system, disregard of BC signs, less support from friends and family, and having first medical examination in a public vs. private medical center. Individual countries differed significantly with regard to intercept of the multilevel models and slopes of regression coefficients for selected psychological and behavioral attributes. Conclusions. An extensive set of variables potentially impacting delay times, mainly related to psychological and behavioral patient attributes, was examined. Several of them strongly determined both PDT and SDT, but their strength differed between individual countries. Both models (for PDT and SDT), although statistically significant, accounted for approximately 20% of variance in time; therefore other variables, e.g. related to the differences in national healthcare systems (not addressed in this study) might have a stronger impact on delays in the initiation of BC therapy and warrant further analyses. [ABSTRACT FROM AUTHOR]