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Bevacizumab (Avastin)

Bevacizumab is a monoclonal antibody that binds to a specific protein called vascular endothelial growth factor (VEGF). The VEGF 'pathway' has an important role in the formation of new blood vessels, which tumours need to develop in order to grow. Because Bevacizumab binds to VEGF it prevents it from activating the VEGF receptor and therefore slows down the growth of new blood vessels via this pathway, in both tumour and normal tissues. As such it is classed as an Angiogenesis Inhibitor

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Web Resources: Bevacizumab (Avastin)
Latest Research Publications

Web Resources: Bevacizumab (Avastin) (6 links)

Latest Research Publications

Bai L, Wang F, Li ZZ, et al.
Chemotherapy plus bevacizumab versus chemotherapy plus cetuximab as first-line treatment for patients with metastatic colorectal cancer: Results of a registry-based cohort analysis.
Medicine (Baltimore). 2016; 95(51):e4531 [PubMed] Free Access to Full Article Related Publications
The present observational cohort study was designed to elucidate the efficacy and safety profile of bevacizumab or cetuximab with chemotherapy as the first-line treatment in Chinese patients with metastatic colorectal cancer (mCRC). Clinical data were collected from a single-center registry study where mCRC patients received first-line fluoropyrimidine-based chemotherapy combined with either bevacizumab (188 patients with KRAS wild-type or mutated tumors) or cetuximab (101 patients with KRAS wild-type tumors) between January 2009 and December 2013. The Kaplan-Meier method was used for survival analysis. Cox proportional hazards model was used for estimating the prognostic and predictive values of clinicopathological characteristics. No statistically significant difference was observed between the bevacizumab and cetuximab groups in terms of median progression-free survival (PFS) (10.6 vs 8.7 months, P = 0.317), median overall survival (OS) (27.7 vs 28.3 months, P = 0.525), or overall response rate (43.1% vs 53.5%, P = 0.108). For the subset of patients with peritoneal dissemination, bevacizumab-based triplet appears to be superior to cetuximab-based triplet as measured by PFS (9.6 vs 6.1 months) and OS (26.3 vs 12.7 months), but not for patients without peritoneal dissemination (PFS, 10.6 vs 9.1 months; OS, 27.9 vs 30.7 months) (all unadjusted and adjusted interaction P < 0.05). Our study suggests that bevacizumab- or cetuximab-based regimens have similar effectiveness as first-line treatment of mCRC in Chinese population. Patients with peritoneal dissemination were likely to gain more benefit from bevacizumab than cetuximab treatment. Future prospective studies are required to further confirm these results.

Netto JP, Schwartz D, Varallyay C, et al.
Misleading early blood volume changes obtained using ferumoxytol-based magnetic resonance imaging perfusion in high grade glial neoplasms treated with bevacizumab.
Fluids Barriers CNS. 2016; 13(1):23 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Neovascularization, a distinguishing trait of high-grade glioma, is a target for anti-angiogenic treatment with bevacizumab (BEV). This study sought to use ferumoxytol-based dynamic susceptibility contrast magnetic resonance imaging (MRI) to clarify perfusion and relative blood volume (rCBV) changes in glioma treated with BEV and to determine potential impact on clinical management.
METHODS: 16 high grade glioma patients who received BEV following post-chemoradiation radiographic or clinical progression were included. Ferumoxytol-based MRI perfusion measurements were taken before and after BEV. Lesions were defined at each timepoint by gadolinium-based contrast agent (GBCA)-enhancing area. Lesion volume and rCBV were compared pre and post-BEV in the lesion and rCBV "hot spot" (mean of the highest rCBV in a 1.08 cm(2) area in the enhancing volume), as well as hypoperfused and hyperperfused subvolumes within the GBCA-enhancing lesion.
RESULTS: GBCA-enhancing lesion volumes decreased 39% (P = 0.01) after BEV. Mean rCBV in post-BEV GBCA-enhancing area did not decrease significantly (P = 0.227) but significantly decreased in the hot spot (P = 0.046). Mean and hot spot rCBV decreased (P = 0.039 and 0.007) when post-BEV rCBV was calculated over the pre-BEV GBCA-enhancing area. Hypoperfused pixel count increased from 24% to 38 (P = 0.007) and hyperperfused decreased from 39 to 28% (P = 0.017). Mean rCBV decreased in 7/16 (44%) patients from >1.75 to <1.75, the cutoff for pseudoprogression diagnosis.
CONCLUSIONS: Decreased perfusion after BEV significantly alters rCBV measurements when using ferumoxytol. BEV treatment response hinders efforts to differentiate true progression from pseudoprogression using blood volume measurements in malignant glioma, potentially impacting patient diagnosis and management.

Chen H, Zhang L, Long X, et al.
Sargassum fusiforme polysaccharides inhibit VEGF-A-related angiogenesis and proliferation of lung cancer in vitro and in vivo.
Biomed Pharmacother. 2017; 85:22-27 [PubMed] Related Publications
Sargassum fusiforme (Harv.) is a brown alga belonging to the Sargasaceae family. The Sargassum fusiforme polysaccharides (SFPS) have demonstrated good anti-tumor and immunomodulatory activity. However, the underlying mechanisms of its anti-tumorigenesis, especially the anti-angiogenic activity is yet to be established. In the present study, we attempted to determine the effects of SFPS on the human lung adenocarcinoma SPC-A-1 cells and its xenograft model. The results showed that SFPS provides a concentration-dependent inhibition of SPC-A-1 cell proliferation in in vitro and the tumor growth in in vivo studies. Immunohistochemistry studies revealed that the administration of SFPS significantly decreased CD31, VEGF-A expression and the tumor microvessel density (MVD). SFPS also provided a dose-dependent impairment of cell vitality, induction of cell cycle arrest and apoptosis of human umbilical vein endothelial cells (HUVECs). SFPS inhibited the expression of VEGF-A in tumor cells and its receptor VEGFR2 in HUVECs. The HUVEC tube formation assay showed that SFPS could abrogate the tube formation with relatively decreased tubes length of tube-like capillary similar to anti-VEGF antibody, Avastin(®). These findings suggested that SFPS could be used as an alternative anticancer drug as they inhibited the angiogenesis and the microvessel formation through disruption of VEGF signals apart from direct tumor cytotoxicity.

Qi N, Li F, Li X, et al.
Combination use of paclitaxel and avastin enhances treatment effect for the NSCLC patients with malignant pleural effusion.
Medicine (Baltimore). 2016; 95(47):e5392 [PubMed] Free Access to Full Article Related Publications
The current study is conducted to investigate efficacy of the chemotherapy drug paclitaxel in combination with Avastin (Roche Diagnostics GmbH., Mannheim, Germany) (antiangiogenic agent) in treatment of malignant pleural effusions (MPEs).Twenty-four patients with non-small cell lung cancer were randomly assigned for 2 treatment approaches. Ten patients received paclitaxel (175 mg/m) alone, and 14 patients took a combination therapy of paclitaxel and Avastin (5 mg/kg). Efficacy of the treatment approaches in the patients was validated with the change in the MPE volume. Pharmacokinetic (PK) profile and urinary excretion rate of paclitaxel were analyzed with serum vascular endothelial growth factor (VEGF) level, and adverse events were examined as well.The combination therapy reduced the MPE level with a successful rate of 29% and a survival rate of 25% over the single paclitaxel treatment in the study cohort (both P < 0.05). PKs for the combined treatment displayed a rapid distribution of the anticancer drug paclitaxel with an obvious increase in its elimination half-life in the pleural fluid (both P < 0.01). Mean residence time of paclitaxel increased in the presence of Avastin (P < 0.01). Serum VEGF levels significantly reduced in the Avastin-treated patients as compared to the paclitaxel-treated ones (P < 0.01). The urinary excretion rate was similar in the study cohort. Incidence of adverse events for the 2 treatment approaches was similar in the patients.Intervention of Avastin enhances potency of paclitaxel in treatment of MPEs with the increased survival rate of the patients through inhibiting VEGF production and prolonging time of ongoing interaction between the chemotherapy drug and the tumor tissues.

Zhou M, Yu P, Qu J, et al.
Efficacy of Bevacizumab in the First-Line Treatment of Patients with RAS Mutations Metastatic Colorectal Cancer: a Systematic Review and Network Meta-Analysis.
Cell Physiol Biochem. 2016; 40(1-2):361-369 [PubMed] Related Publications
BACKGROUND/AIMS: Whether patients with RAS mutation metastatic colorectal cancer (mCRC) obtain benefits from bevacizumab added to first-line chemotherapy remains unclear.
METHODS: PubMed, Cochrane Systematic Reviews, the Cochrane Collaboration Central Register of Controlled Clinical Trials, ClinicalTrials.gov, and the American Society of Clinical Oncology and European Society for Medical Oncology databases were searched to identify abstracts for randomized controlled trials (RCTs) evaluating the efficacy of bevacizumab for the first-line treatment of patients with RAS mutations mCRC from inception to the end of April 2016. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were estimated.
RESULTS: Ten eligible papers reporting six RCTs were included. In the network meta-analysis of patients with RAS mutations, bevacizumab + chemotherapy prolonged PFS compared with chemotherapy alone (HR 0.75, 95% CI 0.51-1.10), but the difference was not statistically significant. Bevacizumab + chemotherapy did not prolong OS compared with chemotherapy alone (HR 1.10, 95% CI 0.73-1.66).
CONCLUSION: There was insufficient evidence to definitively state that patients with RAS mutations mCRC could benefit from bevacizumab combined with chemotherapy as first-line treatment.

Chen K, Gong Y, Zhang Q, et al.
Efficacy and safety of addition of bevacizumab to FOLFIRI or irinotecan/bolus 5-FU/LV (IFL) in patients with metastatic colorectal cancer: A meta-analysis.
Medicine (Baltimore). 2016; 95(46):e5221 [PubMed] Free Access to Full Article Related Publications
Recent studies have paid much attention on the safety of bevacizumab as adjuvant chemotherapy for metastatic colorectal cancer. The aim of this meta-analysis was to study the efficacy and safety of bevacizumab in combination with irinotecan, bolus followed by infusional 5-fluorouracil, and leucovorin (FOLFIRI) and, irinotecan, bolus fluorouracil, leucovorin (IFL) for patients with metastatic colorectal cancer (mCRC).An electronic search of related trials was conducted from PubMed, EMBASE, Cochrane Library databases. Risk ratio (RRs) and its 95% confidence intervals (95% CIs) were calculated by using either DerSimonian-Laird method or Mantel-Haenszel method according to the heterogeneity of included articles. The risk of mortality, therapeutic efficacy, and adverse effect were meta-analyzed.In total, 6 RCTs including 2165 participants (1109 in the treatment group, 1056 in the control group) were included in this meta-analysis. Compared with FOLFIRI-panitumumab/cetuximab, the bevacizumab addition significantly reduced the complete response (CR) rate (RR [95%CI] = 0.31[0.11, 0.89], P = 0.03) and the risk of grade 3/4 adverse event (RR [95%CI] = 0.89[0.80, 0.98], P = 0.01). Compared with FOLFIRI and IFL alone, the addition of bevacizumb significantly increased the partial response (PR) and objective response (OR) rates. Compared with IFL alone, the addition of bevacizumb significantly reduced the mortality risk of PFS (RR [95%CI] = 0.53[0.42, 0.66], P < 0.00001) and OS (RR[95%CI] = 0.70[0.60, 0.82], P < 0.00001), but increased the risk of adverse events (RR[95%CI] = 1.14[1.06, 1.21], P = 0.0002).Combination chemotherapy of bevacizumab plus FOLFIRI or IFL had a relative high efficacy and acceptable safety for treatment of mCRC.

Alt M, Truant S, Renaud-Vantroys T, et al.
Bevacizumab Associated with Chemotherapy for Initially Non-resectable Liver Metastases from Colorectal Cancer: a Case-Control Study.
Anticancer Res. 2016; 36(10):5551-5555 [PubMed] Related Publications
BACKGROUND: The place of bevacizumab in therapy of patients with initially non-resectable liver metastases from colorectal cancer (CRC) remains debated. Bevacizumab may increase the efficacy of chemotherapy but it may also maintain dormant micrometastases in a dormant state, eventually increasing the long-term likelihood of tumor relapse. The aim of this study was to explore this hypothesis.
PATIENTS AND METHODS: A retrospective case-control study was performed in patients with initially non-resectable CRC liver metastases. Metastases were rendered resectable after chemotherapy with (cases) or without (controls) bevacizumab. Cases and controls were matched for synchronicity, number and maximal size of metastases. The main objective was the disease-free survival (DFS).
RESULTS: A total of 82 patients were enrolled (41 in each group). The median DFS was 12.0 months in the bevacizumab group, and 10.2 months in the group treated with chemotherapy alone (p=0.26).
CONCLUSION: We observed no significant effect on DFS for bevacizumab when added to chemotherapy in patients with initially non-resectable liver metastases. Prospective trials on this issue are warranted.

Musella A, Vertechy L, Romito A, et al.
Bevacizumab in Ovarian Cancer: State of the Art and Unanswered Questions.
Chemotherapy. 2017; 62(2):111-120 [PubMed] Related Publications
Ovarian cancer is a most lethal gynecologic tumor. The mainstay treatment is cytoreductive surgery followed by platinum-based chemotherapy. However, a high percentage of patients recur, thus needing multiple treatments with a frequently poor prognosis. In the last two decades, research has focused on the potential of target therapies to improve the survival of patients affected by ovarian cancer. Bevacizumab is one of the most studied target therapies, and it is approved for first- and second-line treatment of advanced epithelial ovarian, fallopian tube, and primary peritoneal tumors. Despite its widespread use with favorable results, controversy regarding patient selection and the best schedule, dosage, and timing of bevacizumab still exists. This review summarizes the state of the art on the use of bevacizumab for ovarian cancer in front-line, recurrence, and neoadjuvant settings. This study focuses on the results of pivotal trials, emerging data, ongoing research, and still unanswered questions about the most adequate dosage of bevacizumab and its potential activity after disease progression or rechallenge in previously treated patients.

Matsushima S, Sato T, Nishiofuku H, et al.
Equivalent cross-relaxation rate imaging and diffusion weighted imaging for early prediction of response to bevacizumab-containing treatment in colorectal liver metastases-preliminary study.
Clin Imaging. 2017 Jan - Feb; 41:1-6 [PubMed] Related Publications
PURPOSE: To evaluate and compare the usefulness of equivalent cross-relaxation rate (ECR) imaging (ECRI) and diffusion-weighted imaging (DWI) in the early prediction of the response of bevacizumab-containing treatments of colorectal liver metastases.
METHODS AND MATERIAL: Seven patients received bevacizumab-containing treatments for colorectal liver metastases. Serial magnetic resonance imaging was performed to evaluate responses before and 2 weeks after starting chemotherapy. In the ECRI, we adopted the off-resonance technique for preferential saturation of immobile protons to evaluate the ECR values. A single saturation transfer pulse frequency was used at a frequency of 3.5 ppm downfield from the water resonance. In the DWI, the apparent diffusion coefficient (ADC) value commonly used with two b-values was acquired by using diffusion weightings of 0 and 800 s/mm(2). The region of interest of the metastatic lesions in the liver was separately measured by ECRI and DWI. Tumor response was assessed by response evaluation criteria in solid tumors criteria 8 weeks after starting chemotherapy.
RESULTS: In this study, we had four responders and three nonresponders. There was a significant difference in the pretreatment ECR values between the responders and nonresponders (P=.01); there was no significant difference in the ADC values between the two groups. Analysis of the percentage difference between the pretreatment and post-treatment values, termed as percentage change, showed that there were no significant differences in the percentage change of the ADC values between both groups; however, the percentage change in the ECR value was significantly greater for the responders than for the nonresponders (-41.6%±17.1% vs. -12.9%±6.9%, respectively; P=.04).
CONCLUSION: The pretreatment ECR value and percentage change of the ECR value 2 weeks after starting chemotherapy were useful parameters in the early prediction of response to bevacizumab-containing treatment in colorectal liver metastases.

Goto K, Endo M, Kusumoto M, et al.
Bevacizumab for non-small-cell lung cancer: A nested case control study of risk factors for hemoptysis.
Cancer Sci. 2016; 107(12):1837-1842 [PubMed] Free Access to Full Article Related Publications
Potentially life-threatening, serious hemoptysis is an adverse event associated with bevacizumab in non-squamous non-small-cell lung cancer (NSCLC) trials. Suggested risk factors include central tumor location and cavitation; however, the profile of hemoptysis occurrence in clinical practice is still unclear. A nested case-control study was conducted to assess the onset profile and risk factors for hemoptysis in bevacizumab-treated patients in a real-world setting in Japan. After bevacizumab was approved for NSCLC, physicians registered all NSCLC patients scheduled for bevacizumab therapy, from November 2009 to August 2011. Patients developing grade 2 hemoptysis requiring an injectable hemostatic agent or grade ≥3 hemoptysis were selected as case subjects, matched with four control subjects each. Case report forms were collected after an observation period of 24 weeks. Radiologists assessed blinded thoracic images. Risk factors for hemoptysis were assessed by univariate and stepwise multivariate analysis. Of 6774 patients registered, 23 (0.3%) experienced grade ≥2 drug-related hemoptysis. A total of 104 patients (21 cases, 83 controls) were analyzed by central reviewers for risk factors of hemoptysis occurrence. In the univariate analysis seven factors were associated with hemoptysis. In the step-wise multivariate analysis, prior thoracic radiotherapy (P = 0.1844), presence of tumor exposure in the central airway (P = 0.0256) and concomitant radiotherapy (P = 0.1169) were identified as risk factors for hemoptysis. While the incidence of hemoptysis was low in the real-world setting in Japan, the three risk factors identified, prior thoracic radiotherapy, presence of tumor exposure in the central airway and concomitant radiotherapy, should be considered when selecting patients for bevacizumab treatment. Although technically classed as a clinical trial, a nested case-control study was a non-interventional surveillance study analyzing all NSCLC patients receiving bevacizumab in Japan, therefore it was not registered as a phase II/III clinical trial would be.

Huang CW, Yeh YS, Ma CJ, et al.
Patients with Metastatic Colorectal Cancer and Hyperbilirubinemia Treated with FOLFIRI plus Bevacizumab as First-Line Treatment.
Chemotherapy. 2017; 62(1):80-84 [PubMed] Related Publications
Metastatic colorectal cancer (mCRC) combined with hyperbilirubinemia is typically considered a contraindication to irinotecan-based therapy, a proven first-line treatment of mCRC. Herein, we present 6 consecutive patients with mCRC combined with hyperbilirubinemia who underwent UGT1A1 genotyping before receiving FOLFIRI plus bevacizumab. Dose escalation of irinotecan was performed according to the results of UGT1A1 genotyping in all patients. Improvement in the serum total bilirubin level to a normal range was noted in all 6 patients. Disease control was 100%. The median progression-free survival was 7.5 months and the median overall survival was 8.5 months. FOLFIRI plus bevacizumab as a first-line chemotherapy may achieve effective disease control and be safe in patients with mCRC and hyperbilirubinemia based on UGT1A1 genotyping. More prospective clinical studies are necessary to evaluate the clinical benefits and safety of this treatment approach.

Sini V, Cassano A, Corsi D, et al.
Bevacizumab as first-line treatment in HER2-negative advanced breast cancer: pros and cons.
Tumori. 2016; 102(5):472-480 [PubMed] Related Publications
PURPOSE: Bevacizumab, a humanized, anti-vascular endothelial growth factor-A monoclonal antibody, has shown efficacy in a number of cancers. However, its use in metastatic breast cancer (MBC) remains controversial.
METHODS: A literature review using the PubMed database was performed to update the currently available clinical trials evidence on bevacizumab in the first-line treatment of breast cancer. In addition, the proceedings of selected oncology annual meetings were searched for relevant presentations.
RESULTS: This article reviews the available evidence for bevacizumab as first-line therapy for MBC and discusses its current and future applicability in the management of MBC. Three phase III trials (ECOG-2100, AVADO, RIBBON-1) demonstrated that the addition of bevacizumab to chemotherapy is well-tolerated and improves progression-free survival and objective response rates in the first-line setting. These findings were supported by a large clinical practice-based study (ATHENA) and a recent clinical trial in which bevacizumab added to paclitaxel showed notable activity in triple-negative MBC. However, bevacizumab has thus far not demonstrated a significant benefit in overall survival.
CONCLUSIONS: The addition of bevacizumab to chemotherapy is well-tolerated and produces substantial improvements in overall response rate and progression-free survival, compared with chemotherapy alone, in advanced HER2-negative breast cancer. Nevertheless, it has thus far not demonstrated a significant benefit in overall survival. Whether prolongation of progression-free survival is enough to consider bevacizumab efficacious is unclear. Based on the available clinical trials results, bevacizumab is a part of the complex therapeutic strategy of advanced HER2-negative breast cancer.

Bertelli G, Drews F, Lutchman-Singh K
Bevacizumab for Ovarian Cancer at High Risk of Progression: Reproducibility of Trial Results in 'Real-world' Patients.
Anticancer Res. 2016; 36(9):4947-50 [PubMed] Related Publications
Bevacizumab has become a 'community standard' at many UK centres as part of first-line treatment of patients with ovarian cancer at high risk of progression [International Federation of Gynecology and Obstetrics (FIGO) stage IV, or suboptimally debulked stage III] based on the results of phase III trials such as ICON-7. Its impact in patients treated outside clinical trials is, however, still unknown. In this study, we investigated patient characteristics, treatment patterns, adverse events and progression-free survival in 'real-world' patients in South West Wales. A total of 60 patients, treated between 2012 and 2015, were included in the study. Patient characteristics were less favourable compared to the bevacizumab-treated high-risk group in the ICON-7 trial (median age: 66 vs. 60 years; stage IV: 58% vs. 42%; performance status 0: 18% vs. 41%); 75% had received neoadjuvant chemotherapy before starting bevacizumab. After a median treatment duration of 8 months (range=0-34 months), 45 patients (75%) had experienced disease progression and 34 (56.7%) had died. Median progression-free survival was 16 months (95% confidence interval=14.4-17.6 months). The most common toxicities consisted of proteinuria (66.7%, all grade 1) and grade 1-2 hypertension (15%). Cardiovascular incidents, two of which were fatal, occurred in 6.7% of patients. In conclusion, our study provides encouraging evidence that the routine use of bevacizumab as part of first-line treatment of patients with ovarian cancer at high risk of progression may be associated with outcomes comparable with those obtained in clinical trials.

Wang Z, Liang L, Yu Y, et al.
Primary Tumour Resection Could Improve the Survival of Unresectable Metastatic Colorectal Cancer Patients Receiving Bevacizumab-Containing Chemotherapy.
Cell Physiol Biochem. 2016; 39(3):1239-46 [PubMed] Related Publications
BACKGROUND: The effect of primary tumour resection (PTR) among metastatic colorectal cancer (mCRC) patients remains controversial. Combination chemotherapy with bevacizumab could improve the clinical outcomes of these patients, which might change the importance of PTR in the multi-disciplinary treatment pattern.
METHODS: We performed a non-randomized prospective controlled study of mCRC pts whose performance status (PS) scored ≤2 and who received bevacizumab combination chemotherapy (FOLFOX/XELOX/FOLFIRI) as a first-line therapy. These patients were classified into the PTR group and the IPT (intact primary tumour) group according to whether they underwent PTR before receiving the systemic therapy. The progression free survival (PFS) time and overall survival (OS) time, which were recorded from the start of the primary diagnosis until disease progression and death or last follow-up, were analysed. We also compared severe clinical events (such as emergency surgery, radiation therapy, and stent plantation) between the two groups.
RESULTS: One hundred and nighty-one mCRC pts (108 male patients and 93 female patients) were entered in this prospective observational study. The median age was 57.5 years old. The clinical characteristics (age, gender, performance status, primary tumour site, RAS status, and the number of metastatic organs) did not significantly differ between the two groups. The median PFS and OS times of the PTR group were superior than those of the IPT group (10.0 vs 7.8 months, p < 0.01 and 22.5 vs 17.8 months, p < 0.01, respectively). The incidences of adverse events associated with systemic therapy were similar between the two groups. Specifically, sixteen patients (21.9%, 16/73) with IPT developed significant primary tumour-related complications, such as bleeding, obstruction or even perforation. Among these patients, five underwent emergency surgery, three patients received a stent, and eight patients underwent radiation therapy.
CONCLUSIONS: The mCRC patients who received PTR and bevacizumab combination chemotherapy had better clinical outcomes than patients who did not receive PTR. PTR also decreased the incidence of severe clinical events and improved quality of life.

Boss JD, Lieu P, Tewari A
Effect of treatment of rectal cancer metastasis with intravitreal bevacizumab (Avastin) in patient with subretinal fluid and macular oedema: short-term follow-up.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
We describe the management of subretinal fluid and macular oedema due to colorectal cancer metastasis to the choroid using intravitreal bevacizumab. A patient with grade VI KRAS mutation rectal cancer with metastasis to the lung and cerebellum presented with left eye choroidal metastasis 1 week after being started on the experimental medication KTN3379. After intravitreal bevacizumab administration, the patient had improvement in macular subretinal fluid, but eventually progressed to severe cystoid macular oedema despite monthly intravitreal bevacizumab treatment.

Lu ZH, Peng JH, Wang FL, et al.
Bevacizumab with preoperative chemotherapy versus preoperative chemotherapy alone for colorectal cancer liver metastases: a retrospective cohort study.
Medicine (Baltimore). 2016; 95(35):e4767 [PubMed] Free Access to Full Article Related Publications
This study aimed to assess the efficacy and safety of bevacizumab plus preoperative chemotherapy as first-line treatment for liver-only metastatic colorectal cancer in Chinese patients compared with those of preoperative chemotherapy alone.Patients with histologically confirmed liver-only metastatic colorectal cancer were sequentially reviewed, and received either preoperative chemotherapy plus bevacizumab (bevacizumab group, n = 32) or preoperative chemotherapy alone (chemotherapy group, n = 57). Progression-free survival, response rate, liver resection rate, conversion rate, and safety were analyzed.With median follow-up of 28.7 months, progression-free survival was 10.9 months (95% confidence interval: 8.7-13.1 months) in bevacizumab group and 9.9 months (95% confidence interval: 6.8-13.1 months) in chemotherapy group (P = 0.472). Response rates were 59.4% in bevacizumab group and 38.6% in chemotherapy group (P = 0.059). Overall liver resection (R0, R1, and R2) rate was 68.8% in bevacizumab group and 54.4% in chemotherapy group (P = 0.185). Conversion rate was 51.9% in bevacizumab group and 40.4% in chemotherapy group (P = 0.341). No postoperative complication was observed in all patients.Bevacizumab plus preoperative chemotherapy as first-line treatment for liver-only metastatic colorectal cancer tends to achieve better clinical benefit with controllable safety in Chinese patients.

Zhu X, Tian X, Yu C, et al.
Increased risk of hemorrhage in metastatic colorectal cancer patients treated with bevacizumab: An updated meta-analysis of 12 randomized controlled trials.
Medicine (Baltimore). 2016; 95(34):e4232 [PubMed] Related Publications
BACKGROUND: As an important antivascular endothelial growth factor monoclonal antibody, bevacizumab has been administrated for the treatment of cancer patients. Hemorrhage, one of the common adverse events of angiogenesis inhibitors, sometimes is also fatal and life-threatening. We aimed at determining the incidence and risk of hemorrhage associated with bevacizumab in patients with metastatic colorectal cancer (mCRC).
METHODS: We searched PubMed, EMBASE, and the Web of Science databases for relevant randomized controlled trials (RCTs). The overall incidence, overall relative risk (RR), and 95% confidence interval (CI) were calculated by using a random-effects or fixed-effects model based on the heterogeneity of selected trials.
RESULTS: A total of 10,555 mCRC patients from 12 RCTs were included in our study. The overall incidence of hemorrhage was 5.8% (95% CI 3.9%-7.8%). Bevacizumab significantly increased the overall risk of hemorrhage with an RR of 1.96 (95% CI 1.27-3.02). The RR of all-grade hemorrhage was 2.39 (95% CI 1.09-5.24) and 1.41 (95% CI 1.01-1.97) for high-grade hemorrhage. The risk of hemorrhage associated with bevacizumab was dose-dependent with an RR of 1.73 (95% CI 1.15-2.61) for 2.5 mg/kg/wk and 4.67 (95% CI 2.36-9.23) for 5 mg/kg/wk. More importantly, the RR of hemorrhage for treatment duration (<= 6 months and > 6 months) based on subgroup analysis was 4.13 (95% CI 2.58-6.61) and 1.43 (95% CI 0.96-2.14), respectively.
CONCLUSION: The addition of bevacizumab to concurrent antineoplastic in patients with mCRC significantly increased the risk of hemorrhage. The dose of bevacizumab may contribute to the risk of hemorrhage. And the 1st 6 months of treatment may be a crucial period when hemorrhagic events occur.

Montagnani F, DI Leonardo G, Pino MS, et al.
Progression-free Survival as a Surrogate End-point in Advanced Colorectal Cancer Treated with Antiangiogenic Therapies.
Anticancer Res. 2016; 36(8):4259-65 [PubMed] Related Publications
BACKGROUND: It is not clear if progression-free survival (PFS) is a good surrogate end-point for overall survival (OS) for metastatic colorectal cancer if antiangiogenic therapies are used.
MATERIALS AND METHODS: We investigated randomized controlled trials testing antiangiogenic agents against chemotherapy. Log hazard ratios (HR) for PFS and OS were used to construct linear regression models. The surrogate threshold effect (STE) was calculated.
RESULTS: Thirteen studies and 24 comparison arms were available, including 7,179 patients. This model returned a significant correlation between PFS and OS (R(2)=0.68, p<0.001) with an STE of 0.83. Analysis restricted to first-line gave similar results (R(2)=0.68, p<0.001, STE=0.75).
CONCLUSION: There is a significant correlation between the effect of treatment on PFS and OS. PFS remains a good surrogate end-point for OS even if anti-angiogenic agents are used.

Morris KA, Parry A, Pretorius PM
Comparing the sensitivity of linear and volumetric MRI measurements to detect changes in the size of vestibular schwannomas in patients with neurofibromatosis type 2 on bevacizumab treatment.
Br J Radiol. 2016; 89(1065):20160110 [PubMed] Article available free on PMC after 01/09/2017 Related Publications
OBJECTIVE: To compare the sensitivity of linear and volumetric measurements on MRI in detecting schwannoma progression in patients with neurofibromatosis type 2 on bevacizumab treatment as well as the extent to which this depends on the size of the tumour.
METHODS: We compared retrospectively, changes in linear tumour dimensions at a range of thresholds to volumetric tumour measurements performed using Brainlab iPlan(®) software (Feldkirchen, Germany) and classified for tumour progression according to the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) criteria.
RESULTS: Assessment of 61 schwannomas in 46 patients with a median follow-up of 20 months (range 3-43 months) was performed. There was a mean of 7 time points per tumour (range 2-12 time points). Using the volumetric REiNS criteria as the gold standard, a sensitivity of 86% was achieved for linear measurement using a 2-mm threshold to define progression.
CONCLUSION: We propose that a change in linear measurement by 2 mm (particularly in tumours with starting diameters 20-30 mm, the majority of this cohort) could be used as a filter to identify cases of possible progression requiring volumetric analysis. This pragmatic approach can be used if stabilization of a previously growing schwannoma is sufficient for a patient to continue treatment in such a circumstance.
ADVANCES IN KNOWLEDGE: We demonstrate the real-world limitations of linear vs volumetric measurement in tumour response assessment and identify limited circumstances where linear measurements can be used to determine which patients require the more resource-intensive volumetric measurements.

Puglisi F, Bisagni G, Ciccarese M, et al.
A Delphi consensus and open debate on the role of first-line bevacizumab for HER2-negative metastatic breast cancer.
Future Oncol. 2016; 12(22):2589-2602 [PubMed] Related Publications
To gain consensus on the role of bevacizumab plus paclitaxel as first-line treatment for HER2-negative metastatic breast cancer, a panel of expert oncologists experienced in treating patients with metastatic breast cancer in Italy participated in a Delphi consensus study. The panel reached a full consensus on the efficacy of bevacizumab plus paclitaxel and the clinical meaningfulness of the progression-free survival benefit compared with paclitaxel alone, despite the lack of an overall survival effect in clinical trials. The participants agreed that real-world data support the effectiveness and well-defined safety profile of the regimen. Views on the use of bevacizumab plus paclitaxel in specific patient populations were not unanimous and clinical judgment remains important. Nevertheless, a high level of agreement was reached.

Zhou J, Zhao R, Wen F, et al.
Economic evaluation study (CHEER-compliant): Cost-effectiveness analysis of RAS screening for treatment of metastatic colorectal cancer based on the CALGB 80405 trial.
Medicine (Baltimore). 2016; 95(27):e3762 [PubMed] Article available free on PMC after 01/09/2017 Related Publications
Cetuximab (Cetux)/Bevacizumab (Bev) treatments have shown considerably survival benefits for patients with metastatic colorectal cancer (mCRC) in the last decade. But they are costly. Currently, no data is available on the health economic implications of testing for extended RAS wild-type (wt) prior to Cetux/Bev treatments of patients with mCRC. This paper aimed to evaluate the cost-effectiveness of predictive testing for extended RAS-wt status in mCRC in the context of targeting the use of Cetux/Bev.Markov model 1 was conducted to provide evidence evaluating the cost-effectiveness of predictive testing for KRAS-wt or extended RAS-wt status based on treatments of chemotherapy plus Cetux/Bev. Markov model 2 assessed the cost-effectiveness of FOLFOX plus Cetux/Bev or FOLFIRI plus Cetux/Bev in extended RAS-wt population. Primary base case data were identified from the CALGB 80405 trial and the literatures. Costs were estimated from West China Hospital, Sichuan University, China. Survival benefits were reported in quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) was calculated.In analysis 1, the cost per QALY was $88,394.09 for KRAS-Cetux, $80,797.82 for KRAS-Bev, $82,590.72 for RAS-Cetux, and $75,358.42 for RAS-Bev. The ICER for RAS-Cetux versus RAS-Bev was $420,700.50 per QALY gained. In analysis 2, the cost per QALY was $81,572.61, $80,856.50, $80,592.22, and $66,794.96 for FOLFOX-Cetux, FOLFOX-Bev, FOLFIRI-Cetux, and FOLFIRI-Bev, respectively. The analyses showed that the extended RAS-wt testing was less costly and more effective versus KRAS-wt testing before chemotherapy plus Cetux/Bev. Furthermore, FOLFIRI plus Bev was the most cost-effective strategy compared with others in extended RAS-wt population.It was economically favorable to identify patients with extended RAS-wt status. Furthermore, FOLFIRI plus Bev was the preferred strategy in extended RAS-wt patients.

Horibe Y, Adachi S, Okuno M, et al.
A refractory duodenal ulcer with a biliary-duodenal fistula following the administration of bevacizumab.
Nihon Shokakibyo Gakkai Zasshi. 2016; 113(7):1244-50 [PubMed] Related Publications
A 65-year-old woman with recurrent breast cancer was repeatedly treated with bevacizumab, an anti-VEGF antibody. In addition, she was also frequently prescribed a nonsteroidal anti-inflammatory drug for abdominal pain. Melena was revealed 2 months after the final treatment with bevacizumab, and an endoscopic study revealed a duodenal ulcer (DU) that was resistant to anti-ulcer therapy. A cholangiography identified a biliary-duodenal fistula with bile juice leaking from the ulcer base. Therefore, a biliary stent was placed into the common bile duct for 3 months until the DU healed. This is the first case of a refractory DU with a biliary-duodenal fistula in a patient treated with bevacizumab.

De Castro J, González-Larriba JL, Vázquez S, et al.
Long-term survival in advanced non-squamous NSCLC patients treated with first-line bevacizumab-based therapy.
Clin Transl Oncol. 2017; 19(2):219-226 [PubMed] Related Publications
BACKGROUND/AIM: First-line bevacizumab-based therapies have been shown to improve clinical outcomes in patients with non-squamous non-small-cell lung cancer (NSCLC). We aimed to descriptively analyse patients with non-squamous NSCLC who received a long-term period of maintenance bevacizumab.
PATIENTS AND METHODS: This retrospective study included 104 patients who had already reached a progression-free survival (PFS) of at least 9 months.
RESULTS: Median overall survival and PFS were 30.7 and 15.1 months, respectively. The overall response rate was 83 %. Weight loss ≤5 %, ECOG PS = 0, or low number of metastatic sites seem to be predictive factors of good evolution. The incidence of bevacizumab-related adverse events appeared to be similar as the previous studies.
CONCLUSION: Our findings show that there is a long-term survivor group whom the administration of bevacizumab resulted in a relevant prolongation of response without new safety signals. Due to the population heterogeneity, it was not possible to identify the standardised predictive factors.

Wahid M, Mandal RK, Dar SA, et al.
Therapeutic potential and critical analysis of trastuzumab and bevacizumab in combination with different chemotherapeutic agents against metastatic breast/colorectal cancer affecting various endpoints.
Crit Rev Oncol Hematol. 2016; 104:124-30 [PubMed] Related Publications
Researchers are working day and night across the globe to eradicate or at least lessen the menace of cancer faced by the mankind. The two very frequently occurring cancers faced by the human beings are metastatic breast cancer and metastatic colorectal cancer. The various chemotherapeutic agents like anthracycline, cyclophosphamide, paclitaxel, irinotecan, fluorouracil and leucovorin etc., have been used impressively for long. But the obstinate character of metastatic breast cancer and metastatic colorectal cancer needs more to tackle the threat. So, the scientists found the use of monoclonal antibodies trastuzumab (Herceptin(®)) and bevacizumab (Avastin(®)) for the same. The current study critically investigates the therapeutic potential of trastuzumab and bevacizumab in combination with various chemotherapeutic agents against metastatic breast cancer and metastatic colorectal cancer. To the best of our knowledge, this is the very first critical analysis showing percent wise increase in various positive endpoints like median time to disease progression, median survival, and progression free survival etc. for the treatment of metastatic breast/colorectal cancer using trastuzumab and bevacizumab in combination with different chemotherapeutic agents and provides the rational for the success and failure of the selected monoclonal antibodies.

Ashshi AM, El-Shemi AG, Dmitriev IP, et al.
Combinatorial strategies based on CRAd-IL24 and CRAd-ING4 virotherapy with anti-angiogenesis treatment for ovarian cancer.
J Ovarian Res. 2016; 9(1):38 [PubMed] Article available free on PMC after 01/09/2017 Related Publications
BACKGROUND: A major hurdle incurrent to the human clinical application of conditionally replicative adenovirus (CRAd)-based virotherapy agents is their limited therapeutic efficacy. In this study we evaluated whether arming our previously reported Ad5/3Δ24 CRAd vector containing a 24-base pair deletion in the E1A conserved region 2, which allows selective replication within Rb-p16-deficient tumor cells, to express therapeutic genes could improve oncolytic virus potency in ovarian cancer cells. We choose to assess the therapeutic benefits achieved by virus-mediated expression of interleukin 24 (IL-24), a cytokine-like protein of the IL-10 family, and the inhibitor of growth 4 (ING4) tumor suppressor protein.
RESULTS: The generated CRAd-IL24 and CRAd-ING4 vectors were tested in ovarian cancer cell lines in vitro to compare their replication, yield, and cytotoxic effects with control CRAd Ad5/3∆24 lacking the therapeutic gene. These studies showed that CRAd-IL24 infection resulted in significantly increased yield of infectious particles, which translated to a marked enhancement of virus-induced cytotoxic effects as compared to CRAd-ING4 and non-armed CRAd. Testing CRAd-IL24 and CRAd-ING4 vectors combined together did not revealed synergistic effects exceeding oncolytic potency of single CRAD-IL24 vector. Both CRAds were also tested along with anti-VEGF monoclonal antibody Avastin and showed no significant augmentation of viral cytolysis by anti-angiogenesis treatment in vitro.
CONCLUSIONS: Our studies validated that arming with these key immunomodulatory genes was not deleterious to virus-mediated oncolysis. These findings thus, warrant further preclinical studies of CRAd-IL24 tumoricidal efficacy in murine ovarian cancer models to establish its potential utility for the virotherapy of primary and advanced neoplastic diseases.

Tamburini E, Rudnas B, Santelmo C, et al.
Maintenance based Bevacizumab versus complete stop or continuous therapy after induction therapy in first line treatment of stage IV colorectal cancer: A meta-analysis of randomized clinical trials.
Crit Rev Oncol Hematol. 2016; 104:115-23 [PubMed] Related Publications
BACKGROUND: In stage IV colorectal cancer, bevacizumab-based maintenance therapy, complete stop therapy and continuous therapy are considered all possible approaches after first line induction chemotherapy. However, there are no clear data about which approach is preferable.
MATERIAL AND METHODS: All randomized phase III trials comparing bevacizumab-based maintenance therapy (MB) with complete stop therapy (ST) or with continuous therapy (CT) were considered eligible and included into the analysis. Primary endpoint was the Time to failure strategies (TFS). Secondary endpoints were Overall Survival (OS) and Progression free survival (PFS). Meta-analysis was performed in line with the PRISMA statement.
RESULTS: 1892 patients of five trials were included into the analysis. A significant improvement in TFS (HR 0.79; CI 95% 0.7-0.9 p=0.0005) and PFS (HR 0.56; CI 95% 0.44-0.71 p<0.00001) were observed in favour of MB versus ST. A trend, but not statistically significant, in favour of MB versus ST was also observed for OS (HR 0.88; CI 95% 0.77-1.01, p=0.08). Comparing maintenance therapy versus continuous therapy no statistically differences were observed in the outcomes evaluated (OS 12 months OR 1.1 p=0.62, OS 24 months OR 1 p=1, OS 36 months OR 0.54 p=0.3, TFS 12 months OR 0.76 p=0.65).
CONCLUSIONS: Our meta-analysis suggests that use of MB approach increases TFS, PFS compared to ST. Although without observing any statistically advantage, it should be highlighted that MB versus ST showed a trend in favour of MB. We observed no difference between MB and CT. MB should be considered the standard regimen in patients with stage IV colorectal cancer after first line induction therapy.

Schaub C, Schäfer N, Mack F, et al.
The earlier the better? Bevacizumab in the treatment of recurrent MGMT-non-methylated glioblastoma.
J Cancer Res Clin Oncol. 2016; 142(8):1825-9 [PubMed] Related Publications
PURPOSE: The adequate second-line therapy of patients with glioblastoma (GBM) is a matter of ongoing debate. This particularly applies to patients with a non-methylated MGMT promotor who are known to have a poor response to alkylating chemotherapy. In some countries, antiangiogenic therapy with BEV is applied as second-line therapy, and in others nitrosourea therapy is second-line choice. It is an open question whether the delay of BEV to third-line therapy has a negative impact on survival.
METHODS: A total of 61 adult patients (median age 56.9 years) with MGMT-non-methylated relapsed GBM treated with BEV (n = 45) or nitrosourea (n = 16) as second-line therapy were analyzed retrospectively and compared regarding progression-free survival (PFS) and overall survival (OS).
RESULTS: Patients treated with second-line BEV had longer median PFS (107 days, 95 % CI 80.7-133.2 days) than patients with second-line nitrosourea (52 days, 95 % CI 36.3-67.7 days, P = 0.011, logrank test). However, there was no significant difference in overall survival (BEV median 170 days, 95 % CI 87.2-252.8 days; nitrosourea median 256 days, 95 % CI 159.9-352.0 days, P = 0.468). PFS was similar after BEV third-line therapy (median 117 days, 95 % CI 23.6-210.4 days) as compared to second-line BEV therapy (median 107 days, 95 % CI 80.7-133.3 days, P = 0.584).
CONCLUSION: Our findings suggest that early treatment with BEV in patients with MGMT-non-methylated relapsed GBM is associated with a better PFS, but not with superior OS, possibly implicating that the early, i.e., second-line, use of BEV is not mandatory and BEV treatment may safely be delayed to third-line therapy in this subgroup of patients.

Chen J, Smalligan RD, Nadesan S
When a good call leads to a bad connection: colovesical fistula in colorectal cancer treated with bevacizumab.
Hosp Pract (1995). 2016; 44(3):120-2 [PubMed] Related Publications
INTRODUCTION: Colorectal cancer is the third most common cancer in the United States. The use of bevacizumab (Avastin), a vascular endothelial growth factor (VEGF) inhibitor, has been increasing due to observed improvement in metastatic colon cancer survival, but so has the incidence of bowel perforation. We present one unusual complication of bowel perforation, a colovesical fistula in a colorectal cancer patient treated with bevacizumab.
CASE PRESENTATION: A 54-year-old white male diagnosed with Stage IV colorectal cancer was treated with folinic acid, leucovorin, fluorouracil, oxaliplatin (FOLFOX) and bevacizumab. Two months later, he developed pneumaturia and fecaluria. CT showed a rectosigmoid colovesical fistula. A laparoscopic diverting colostomy was created to overcome the proximal retention of feces and the fecaluria.
DISCUSSION: Colovesical fistulas more commonly result from diverticulitis, cancer, or Crohn's, but rarely can arise from radiation or chemotherapy. Our patient had two risk factors, colorectal carcinoma and bevacizumab use. Although colon cancer itself can cause a colovesical fistula, at the time of diagnosis, our patient had an intact fat pad between the colon and bladder on CT and did not have symptoms consistent with a fistula, suggesting that bevacizumab was the culprit. The exact mechanism of action leading to bowel perforation is not completely understood. Three theories include first, the idea that bevacizumab increases the risk of thrombosis, second, that tumor destruction creates an area of weakness more prone to perforation, or third, it slows down wound healing, causing leakage at the anastomotic site following surgery.
CONCLUSION: Hospitalists encounter patients with colorectal cancer on a regular basis, so clinicians must be aware of the uncommon but potentially serious side effect of bowel perforation when bevacizumab is used. This case has illustrated an even more rare complication, the formation of a colovesical fistula that was treated with laparoscopic surgical intervention with a diverting colostomy.

Roh SA, Park IJ, Yoon YS, et al.
Feasibility of novel PPP1R15A and proposed ANXA11 single nucleotide polymorphisms as predictive markers for bevacizumab regimen in metastatic colorectal cancer.
J Cancer Res Clin Oncol. 2016; 142(8):1705-14 [PubMed] Related Publications
PURPOSE: Bevacizumab improves survival in patients with metastatic colorectal cancer (mCRC) under chemotherapy, but few predictive markers have been identified.
METHODS: To investigate chemosensitive single nucleotide polymorphisms (SNPs) of mCRC, we performed exome sequencing and RNA sequencing in 19 patients. A clinical association analysis was performed with the other 116 patients who had received chemotherapy to bevacizumab regimens. In vivo biodistribution studies and [(18)F]FDG-PET imaging were performed on mice bearing human colorectal cancer (HCT116 and SW480) xenografts after injection of bevacizumab with 5-FU, leucovorin, and irinotecan (FOLFIRI).
RESULTS: PPP1R15A rs557806 showed the most significant association with FRB-driven tumor IR in exome sequencing and the highest correlation (r = 0.74) with drug responses in RNA sequencing. Patients homozygous for the reference alleles (GG) of PPP1R15A rs557806 exhibited greater disease control rate and a tendency toward greater objective response rate (ORR) than those with homozygous or heterozygous substitution alleles (GC and CC; P = 0.027 and 0.073, respectively). In xenografted mice, HCT116 clones transfected with the G allele at PPP1R15A rs557806 were more sensitive to bevacizumab regimens than those with the C allele. Tumor volume of xenografts with the G allele was significantly lower than that of xenografts with the C allele (P = 0.004, day 13). [(18)F]FDG uptake decreased to 75 % in HCT116 xenograft-bearing mice with the G allele, whereas [(18)F]FDG uptake was 42 % in mice xenografts with the C allele (P = 0.032). ANXA11 rs1049550, a predictive biomarker of SNP described in our previous study, was validated using the xenograft model. Tumor volume and [(18)F]FDG uptake analyses showed that tumors in the SW480 xenografts expressing the substitution allele (T) at ANXA11 rs1049550 were more susceptible to FOLFIRI plus bevacizumab-induced suppression than those expressing the reference allele (C) (P = 0.001 and 0.026, respectively).
CONCLUSION: ANXA11 rs1049550 and PPP1R15A rs557806 may improve the identification of mCRC patients sensitive to bevacizumab regimens, and further validation is required in large cohorts.

Marín-Pozo JF, Duarte-Pérez JM, Sánchez-Rovira P
Safety, Effectiveness, and Costs of Bevacizumab-Based Therapy in Southern Spain: A Real World Experience.
Medicine (Baltimore). 2016; 95(19):e3623 [PubMed] Article available free on PMC after 01/09/2017 Related Publications
To evaluate the safety and efficacy of bevacizumab in a broader patient population with solid tumors in the context of general clinical practice. Moreover, we quantified the economic impact and characterized the off-label use (OLU) of this agent in real-life prescribing practices.This is an open, retrospective, observational, real world study carried out at a regional Spanish hospital attending a population of 665,000 inhabitants. All of the patients receiving bevacizumab-containing therapy between January 2006 and February 2012 at the study hospital were included: no exclusion criteria were specified. All study variables were collected from available hospital records.The analysis comprised 240 episodes from 226 patients (male 41%; median age 57 years, 25% ≥65 years). Eighty cases (33%) of bevacizumab treatment were administered as first-line therapy. The median duration of bevacizumab treatment was 5.8 months (95% CI 5.1-6.6), without difference by age, line of treatment, or type of tumor. Typically bevacizumab-related toxicities included bleeding (25%), hypertension (5%), wound-healing complications (4%), gastrointestinal perforation (2%), and arterial thromboembolism (1%). Median progression-free survival was 7.5 months (95% CI 6.3-8.7) and median OS reached 13.1 months (95% CI 11.4-14.9). Bevacizumab increased the chemotherapy cost to 207% (from &OV0556;3,115,615 to &OV0556;9,552,405). Bevacizumab was prescribed off-label in 43% of episodes, amounting to &OV0556;3,586,420 (56% of bevacizumab total cost).The efficacy and safety profile of bevacizumab in routine clinical practice is consistent with results observed in prospective randomized clinical trials. OLU of this drug should be closely monitored.

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