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BACKGROUND Bevacizumab is associated with an increased risk of arterial thromboembolism (ATE); however, its effect on venous thromboembolism (VTE) remains controversial. Scant data exist on the factors that increase the risk of ATE/VTE in patients with prostate cancer. The authors investigated the association of bevacizumab treatment and clinical factors with ATE/VTE risk in patients who were treated on Cancer and Leukemia Group B (CALGB) trial 90401. METHODS Patients with metastatic, castration-resistant prostate cancer were randomized to receive docetaxel and prednisone with or without bevacizumab once every 21 days. Cycle-to-event Cox regression models were used to investigate the association of bevacizumab with the incidence of grade 3 or greater (≥3) ATE and VTE. Age, prior ATE/VTE, baseline antiplatelet/anticoagulant use, and VTE risk score (based on leukocyte count, hemoglobin, platelet count, body mass index, and tumor location) were evaluated in univariate and multivariable analyses. RESULTS Of 1008 randomized patients, the odds of experiencing grade ≥3 ATE were significantly greater in those who received bevacizumab compared with those who received placebo (odds ratio, 2.79; P = .02), whereas an opposite trend was noted for grade ≥3 VTE (odds ratio, 0.60; P = .08). In the multivariable analysis, bevacizumab treatment (hazard ratio [HR], 3.00; P = .01) and age (HR, 1.06; P = .02) were significantly associated with the risk of ATE; whereas age (HR, 1.05; P = .01) and VTE risk score (HR, 1.83; P = .03) were significantly associated with the risk of VTE. CONCLUSIONS Bevacizumab was significantly associated with a greater risk of ATE in patients with metastatic, castration-resistant prostate cancer, but it was not significantly associated with the risk of VTE. Understanding clinical factors that increase the risk for experiencing ATE/VTE is essential to mitigate the risks and reduce the burden of these prevalent complications in cancer care. Cancer 2015;121:1025-1031. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND The current study was conducted to investigate the dependence between progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) and to explore whether PFS can be used as an intermediate endpoint of OS in this patient population. METHODS A total of 1381 patients from 2 prospective phase 3 trials (Cancer and Leukemia Group B [CALGB] 90206 and AVOREN) of interferon-alpha with or without bevacizumab were analyzed. Both trials recruited previously untreated patients with clear cell mRCC with an Eastern Cooperative Oncology Group performance status of 0 to 2; adequate bone marrow, hepatic, cardiac, and renal function; and controlled blood pressure. The CALGB study served as the training data set, and the AVOREN study served as the testing data set. The dependence between PFS and OS was investigated using the Kendall tau for bivariate time-to-event endpoints. RESULTS In the training data set, the median OS times among patients who experienced progressive disease at 3 months or 6 months were 6 months and 8 months, respectively, compared with 25 months and 30 months, respectively, ( P < .001) in patients who did not develop disease progress. The adjusted hazard ratios (HR) were 2.6 ( P < .0001) and 2.8 ( P < .0001), respectively, for patients who did and did not progress at 3 months or 6 months. The dependence between PFS and OS was 0.53. These associations were confirmed in the testing data set. CONCLUSIONS In patients with mRCC who were treated with interferon-alpha with or without bevacizumab, the PFS at 3 months and 6 months was found to be predictive of OS. A high dependence between PFS and OS was observed, suggesting that PFS may be used as a surrogate endpoint for OS. Although this is a novel observation for RCC, these findings require validation in patients with mRCC who are treated with other targeted agents. Cancer 2014;120:52-60. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The use of docetaxel prolongs survival for patients with castrate-resistant prostate cancer (CRPC). Inhibition of vascular endothelial growth factor (VEGF) with bevacizumab may further enhance the antitumor effect of docetaxel and estramustine in patients with CRPC. METHODS: This cooperative group trial enrolled men with CRPC. Patients received oral estramustine 280 mg 3 times daily on Days 1 through 5 of every cycle plus 70 mg/m² docetaxel and 15 mg/kg bevacizumab on Day 2 every 3 weeks. Prostate-specific antigen (PSA) values were monitored every cycle, and imaging studies were obtained every 3 cycles. The primary endpoint was progression-free survival (PFS), and the secondary objectives were safety, PSA decline, measurable disease response, and overall survival. RESULTS: Seventy-nine patients were enrolled; and 77 patients received a median of 8 cycles and were evaluable. A 50% PSA decline was observed in 58 patients (75%). Twenty-three of 39 patients with measurable disease had a partial response (59%). The median PFS was 8 months, and the overall median survival was 24 months. Neutropenia without fever (69%), fatigue (25%), and thrombosis/emboli (9%) were the most common severe toxicities. Twenty-four of 77 patients were removed from protocol treatment because of disease progression, 35 of 77 patients were removed because of a physician or patient decision, and 15 patients were removed secondary to toxicity. CONCLUSIONS: The combination of docetaxel, estramustine, and bevacizumab was tolerable but complicated by toxicity. Although the endpoint of PFS did not meet the desired level, encouraging antitumor activity and overall survival were observed. Further phase 3 evaluation of the role of bevacizumab in CRPC is ongoing. [ABSTRACT FROM AUTHOR]