Bevacizumab-containing Chemotherapy Research Articles

Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1.

Bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, inhibits angiogenesis and reduces tumor growth. Serum VEGF-C, lactate dehydrogenase, and inflammatory markers have been reported as predictive markers related to bevacizumab treatment. Programmed cell death ligand 1 (PD-L1) could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis. To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer (CRC) according to the expression of PD-L1. This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24, 2014 and February 28, 2022, at Samsung Medical Center (Seoul, South Korea). Analysis of patient data included evaluation of PD-L1 expression by the combined positive score (CPS). We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC. A total of 124 patients was included in this analysis. Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy. While 77% of patients received FOLFOX, 23% received FOLFIRI as backbone first-line chemotherapy. The numbers of patients with a PD-L1 CPS of 1 or more, 5 or more, or 10 or more were 105 (85%), 64 (52%), and 32 (26%), respectively. The results showed no significant difference in progression-free survival (PFS) and overall survival (OS) with bevacizumab treatment between patients with PD-L1 CPS less than 1 and those with PD-L1 CPS of 1 or more (PD-L1 < 1% vs PD-L1 ≥ 1%; PFS: P = 0.93, OS: P = 0.33), between patients with PD-L1 CPS less than 5 and of 5 or more (PD-L1 < 5% vs PD-L1 ≥ 5%; PFS: P = 0.409, OS: P = 0.746), and between patients with PD-L1 CPS less than 10 and of 10 or more (PD-L1 < 10% vs PD-L1 ≥ 10%; PFS: P = 0.529, OS: P = 0.568). Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

Hypertension as predictive factor for bevacizumab-containing first-line therapy in metastatic breast and colorectal cancer in BRECOL (GEICAM/2011-04) study

BackgroundRetrospective data suggest an association between bevacizumab efficacy and the incidence of arterial hypertension (AHT). Additionally, epigenetic mechanisms have been related to AHT.MethodsThis prospective observational study conducted by GEICAM Spanish Breast Cancer Research Group included metastatic breast (MBC) or colorectal (mCRC) cancer patients treated with bevacizumab-containing chemotherapy as first-line treatment. Blood pressure (BP) levels were measured (conventional and 24-h Holter monitoring) at baseline and up to cycle 3. Primary endpoint assessed BP levels increase as predictive factor for progression-free survival (PFS). Germline DNA methylation profile was explored in pre-treatment blood samples; principal component analysis was used to define an epigenetic predictive score for increased BP levels.ResultsFrom Oct-2012 to Jul-2016, 143 (78 MBC and 65 mCRC) patients were included. The incidence of AHT according to guidelines was neither predictive of PFS nor of best overall tumor response (BOR). No statistically significant association was observed with systolic BP nor diastolic BP increment for PFS or BOR. Grade 3 and 4 adverse events were observed in 37 and 5% of patients, respectively. We identified 27 sites which baseline methylation status was significantly associated to BP levels increase secondary to bevacizumab-containing chemotherapy.ConclusionsNeither the frequency of AHT nor the increase of BP levels were predictive of efficacy in MBC and mCRC patients treated with bevacizumab-containing chemotherapy.Clinical trial registryClinicalTrials.gov Identifier: NCT01733628.

Serum angiopoietin-like protein 2 level in patients who received bevacizumab-containing chemotherapy for metastatic colorectal cancer.

209 Background: Anti-angiogenic agents are important for treating patients with advanced colorectal adenocarcinoma, however, their efficacy is not long-lasting and survival benefits are modest. Reliable biomarkers and novel targets for angiogenesis are still required in this era. Angiopoietin-like protein 2 (AGLP-2) is an emerging biomarker for angiogenesis in cardiovascular disease, but its role in the oncology area is yet to be elucidated. Methods: Serum samples from patients with advanced colorectal carcinoma treated with bevacizumab-containing chemotherapy were retrospectively studied. Blood samples at baseline and at disease progression of the first line systemic therapy were selected. Serum angiopoietin-like protein 2 (AGLP-2) concentrations were measured using ELISA kit, serial changes, and the relationship with progression-free survival and overall survival on the systemic therapy were statistically analyzed. Results: 68 patients were enrolled. Their median age was 66 years old (range, 38-82), and 14 (20.6%) patients had metastatic lesions at 3 or 4 organs. The median serum AGLP-2 levels at baseline and at disease progression (PD) were 41,618 pg/ml (95% confidence interval (CI) 34,560-40,713), and 49,706 pg/ml (95% CI 39,853-49,017), respectively. There was a tendency of difference between AGLP-2 levels at baseline and at PD ( p=0.057). Patients whose baseline serum AGLP-2 levels with 40,000 pg/ml or above showed relatively shorter overall survival (median 31.4 months with 95% CI, 14.4-38.6) compared with patients with serum AGLP-2 level below 40,000 pg/ml at baseline (median 38.6 months with 95% CI, 23.6-127.3), but not statistically significant ( p=0.0946). There was no survival difference observed according to serum AGLP-2 levels at disease progression on the first line bevacizumab-containing chemotherapy. Conclusions: Serum angiopoietin-like protein-2 has potential as a new target for novel anti-angiogenic therapy in metastatic colorectal cancer.

DDEL-02. CLINICAL BENEFIT OF BEVACIZUMAB AND IRINOTECAN (BEV+IRI) IN PATIENTS WITH RELAPSED/REFRACTORY GLIOBLASTOMA (R/RGBM) AND ITS POTENTIAL PREDICTORS

Abstract BACKGROUND/AIM: Bevacizumab-containing chemotherapy constitutes an important salvage treatment for recurrent/refractory glioblastoma(r/rGBM). Patients and methods: We retrospectively collected the data of r/rGBM patients treated with the combination of bevacizumab and irinotecan (BEV+IRI) as their salvage treatment from July 2013 and December 2021 in Konkuk Medical Center of Korea. Patients with available results from molecular diagnostic tests were eligible, and markers of interest were examined including the presence of MGMT methylation, IDH1/2 mutation, or 1p/19q co-deletion. Efficacy of BEV+IRI and its potential biomarker was explored. RESULTS: Among 21 patients, 38.1% demonstrated European Cooperative Oncology Group-Performance scale (ECOG-PS) ≥3. The majority (71.4%) received BEV+IRI as their second-line chemotherapies, and the median dose was 5 (range=1-25). Objective response rate (ORR) was 33.3% and disease-control rate (DCR) was 85.7%. Irrespective of objective response, early clinical response was achieved in 14(66.7%) patients. During the median follow-up of 16.4 months for survivors, median progression-free survival (PFS) and overall survival (OS) were 3.6 and 6.8 months, respectively. ECOG PS≥3 and TP53 loss were independent predictors of an unfavorable OS, while prompt clinical improvement could predict favorable OS. Any molecular aberration was associated with OS or PFS in the study. CONCLUSION: Salvage BEV+IRI treatment in r/rGBM conferred comparable clinical benefit. ECOG PS ≥3, TP53 loss, and lack of prompt clinical improvement after the treatment were significantly associated with an unfavorable OS.

P45-5 A case report of pneumothorax after treatment with bevacizumab-containing chemotherapy for metastatic breast cancer

P45-5 A case report of pneumothorax after treatment with bevacizumab-containing chemotherapy for metastatic breast cancer

Clinical Benefit of Bevacizumab and Irinotecan (BEV+IRI) in Patients With Relapsed/Refractory Glioblastoma (r/rGBM) and its Potential Predictors.

Bevacizumab-containing chemotherapy constitutes an important salvage treatment for recurrent/refractory glioblastoma(r/rGBM). We retrospectively collected the data of r/rGBM patients treated with the combination of bevacizumab and irinotecan (BEV+IRI) as their salvage treatment from July 2013 and December 2021 in Konkuk Medical Center of Korea. Patients with available results from molecular diagnostic tests were eligible, and markers of interest were examined including the presence of MGMT methylation, IDH1/2 mutation, or 1p/19q co-deletion. Efficacy of BEV+IRI and its potential biomarker was explored. Among 21 patients, 38.1% demonstrated European Cooperative Oncology Group-Performance scale (ECOG-PS) ≥3. The majority (71.4%) received BEV+IRI as their second-line chemotherapies, and the median dose was 5 (range=1-25). Objective response rate (ORR) was 33.3% and disease-control rate (DCR) was 85.7%. Irrespective of objective response, early clinical response was achieved in 14(66.7%) patients. During the median follow-up of 16.4 months for survivors, median progression-free survival (PFS) and overall survival (OS) were 3.6 and 6.8 months, respectively. ECOG PS≥3 and TP53 loss were independent predictors of an unfavorable OS, while prompt clinical improvement could predict favorable OS. Any molecular aberration was associated with OS or PFS in the study. Salvage BEV+IRI treatment in r/rGBM conferred comparable clinical benefit. ECOG PS ≥3, TP53 loss, and lack of prompt clinical improvement after the treatment were significantly associated with an unfavorable OS.

Penetrating complications of bevacizumab-containing chemotherapy in previously-irradiated recurrent cervical cancer: a Korean multicenter retrospective study of the Gynecologic Oncology Research Investigators coLLaborAtion (GORILLA) group (GORILLA1001) (036)

<b>Objectives:</b> Gynecologic Oncology Group 240 study showed that incorporating bevacizumab in the treatment of recurrent, persistent, or metastatic cervical cancer conferred overall survival (OS) benefit. However, fistula occurred significantly higher in the bevacizumab (+) group than the chemotherapy alone group. Moreover, all fistulas in the bevacizumab (+) group were developed in patients who were previously irradiated. This study aimed to evaluate the incidence and to identify risk factors for penetrating complications, including gastrointestinal (GI) and genitourinary (GU) fistula/perforation, of bevacizumab plus chemotherapy in recurrent cervical cancer patients who underwent pelvic radiation therapy (RT). <b>Methods:</b> Medical records of the patients with recurrent cervical cancer who previously underwent pelvic radiation at five university hospitals in Korea from 2007 to 2020 were retrospectively reviewed. Women who received chemotherapy immediately after RT were excluded. Clinical-pathologic factors were compared between groups of the following two settings: <i>1)</i> fistula/perforation (+) and (-); <i>2)</i> bevacizumab plus chemotherapy and chemotherapy alone. Univariate and multivariate regression analyses were performed to identify risk factors for penetrating complications. OS was also compared between groups of the two comparisons. <b>Results:</b> Of 219 women with recurrent cervical cancer who previously underwent pelvic RT, 144 (65.8%) received bevacizumab-containing chemotherapy, and 75 (34.2%) received chemotherapy alone. Fistula/perforation of any grade occurred in 36 (16.4%): fistulas alone in 27 (11 GI, 8 GU, and 8 both) and perforations in nine patients. Women receiving bevacizumab experienced fistula/perforation more frequently than those who used chemotherapy alone (20.8% [30/144] vs 8.0% [6/75]; p=0.015) (Table 1). Multivariate regression analysis showed that bevacizumab administration was the only independent risk factor for the occurrence of fistula/perforation. Age, diabetes, hypertension, tumor histology (squamous vs non-squamous), cumulative dose of RT, primary treatment (operation vs. RT vs both), use of intensity-modulated RT, and the time interval between RT and bevacizumab failed to show association with fistula/perforation. During median follow-up of 33.7 months (1.2-185.6 months), significant OS difference was shown neither between bevacizumab (+) versus bevacizumab (-) (HR: 1.03; median 119.8 months [95% CI: 97.3-142.3months] vs 115.7 months [96.0-135.4 months]; p=0.928) nor between fistula/perforation (+) versus fistula/perforation (-) (HR: 1.78; median 84.2 months [59.3-109.0 months] vs 129.5 months [114.1-144.9 months]; p=0.065). <b>Conclusions:</b> The study results suggest that incorporating bevacizumab in the chemotherapy regimen to treat recurrent cervical cancer with a previous history of pelvic RT incurs a considerable risk of GI and/or GU penetrating complications, which might damage the survival outcome as well as the quality of life. The risk and benefit of incorporating bevacizumab in the treatment of previously irradiated recurrent cervical cancer patients are needed to be carefully weighed, considering that effective prevention of the penetrating complications is difficult because of the lack of knowledge regarding other risk factors.

Pneumothorax as a Complication of Bevacizumab-Containing Chemotherapy: A Systematic Review of Case Reports.

Bevacizumab is a monoclonal anti-vascular endothelial growth factor (VEGF) antibody that binds to and makes all of the VEGF isoforms inactive, and thus prevents angiogenesis, development, and the spread of the tumor. The most reported side effects after administering bevacizumab include bleeding, high blood pressure, heart failure, proteinuria, thrombosis, and gastrointestinal perforation. Pneumothorax has rarely been reported as a complication of bevacizumab, but with an unclear mechanism. This article aims to explore the occurrence of pneumothorax as a side effect after using bevacizumab through a systematic review of current case reports published on the topic. A literature search was conducted using PubMed, Google Scholar, ScienceDirect, and Directory of Open Access through the utilization of appropriate keywords, and case reports were selected based on predefined inclusion and exclusion criteria. Our results encompass five case reports that were further evaluated for demographic, clinical, and treatment parameters. This systematic review concludes that pneumothorax can occur after bevacizumab-containing chemotherapy although this side effect is relatively rare. Awareness regarding this possible side effect can assist clinicians during their practice in considering pneumothorax as a possible differential diagnosis when encountering patients presenting with pulmonary symptoms after starting bevacizumab-containing chemotherapy; hence, timely diagnosis and treatment can save a life.

ASO Visual Abstract: Prediction of Therapeutic Effect of Treatment on Patients with Colorectal Liver Metastases Using Functional Magnetic Resonance Imaging and RECIST Criteria: A Pilot Study Comparing Bevacizumab-Containing Chemotherapy and Standard Chemotherapy

ASO Visual Abstract: Prediction of Therapeutic Effect of Treatment on Patients with Colorectal Liver Metastases Using Functional Magnetic Resonance Imaging and RECIST Criteria: A Pilot Study Comparing Bevacizumab-Containing Chemotherapy and Standard Chemotherapy

Prediction of Therapeutic Effect to Treatment in Patients with Colorectal Liver Metastases Using Functional Magnetic Resonance Imaging and RECIST Criteria: A Pilot Study in Comparison between Bevacizumab-Containing Chemotherapy and Standard Chemotherapy.

Response Evaluation Criteria in Solid Tumors (RECIST) criteria are widely used for evaluating the therapeutic effect of colorectal liver metastases (CRLM) patients, but showed undesirable accuracy. This study aimed to evaluate the value of functional MRI compared with RECIST criteria in predicting the therapeutic effect in CRLM patients receiving neoadjuvant chemotherapy with and without bevacizumab. Overall, 137 patients with CRLM who received neoadjuvant chemotherapy followed by hepatic resection between January 2013 and November 2018 were included and were divided into the bevacizumab and non-bevacizumab groups. Apparent diffusion coefficient (ADC) values of pre- and post-treatment diffusion-weighted imaging (DWI) were generated on the whole-volume (ADCmean), periphery (ADCperi), and isocenter (ADCcentral) of the tumor at the maximum slice. Overall survival (OS) and relapse-free survival (RFS) were used as prognostic indicators. Post-treatment ADCmean was significantly associated with OS (p=0.001) and RFS (p=0.008) in the bevacizumab group, while RECIST-defined response was found to be only significantly associated with RFS in the non-bevacizumab group (p=0.042). When categorizing the bevacizumab group by the post-treatment ADCmean cut-off value of 1.15 ×10-3 mm2/s, patients in the ADC response group showed significantly better OS than the non-response group (3-year OS: 91.5% vs. 64.5%, p=0.001). However, no significant difference was found between RECIST-defined response and non-response in either OS (3-year OS: 60.2% vs. 44.0%, p=0.104) or RFS (3-year RFS: 26.2% vs. 17.4%, p=0.129) in the bevacizumab group. DWI-related parameters such as post-treatment ADCmean could accurately reflect the therapeutic effectiveness and predicting survival in patients treated with bevacizumab, which is superior to the RECIST criteria.

Efficacy and Safety of Bevacizumab in Pretreated Metastatic Breast Cancer: A Systematic Review and Meta-Analysis.

The use of bevacizumab in patients with previously treated metastatic breast cancer (MBC) is controversial. This meta-analysis was carried out to evaluate the efficacy and safety of the regimen including bevacizumab among patients with pretreated MBC. We systematically searched PubMed, the Cochrane Library, Web of Science, and Embase databases for randomized controlled trials evaluating bevacizumab combined with chemotherapy for previously treated MBC patients. The primary endpoints were progression-free survival (PFS) and objective response rate (ORR). The secondary endpoints were overall survival (OS) and toxicity. The risk of bias was assessed by the Cochrane Collaboration's tool. The pooled hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CIs) were calculated for the identified studies. This study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Four studies involving 1,640 individuals were included. Pooling results showed that the PFS of bevacizumab-containing groups (HR 0.82; 95% CI 0.73-0.93, p = 0.002) was significantly better than that of the control groups, especially when bevacizumab was administered as the second-line treatment for patients with human epidermal growth factor receptor 2 (HER2)-negative MBC (HR 0.77; 95% CI 0.66-0.88, p = 0.0002). The ORR in the bevacizumab-containing group was superior to that in the control group, both in the general (RR 1.45; 95% CI 1.18-1.78, p = 0.0004) and HER2-negative groups (RR 1.30; 95% CI 1.03-1.63, p = 0.03). However, no significant effect on OS was demonstrated for the addition of bevacizumab to the second-line treatment for HER2-negative MBC (HR 0.93; 95% CI 0.79-1.10, p = 0.39). Comparatively, proteinuria was more common in the bevacizumab-containing group. In addition, the application of bevacizumab tended to result in therapy discontinuation due to treatment-related toxicity. Bevacizumab-containing chemotherapy, in light of its favorable effects on clinical outcomes, could be a preferred therapeutic option for patients with MBC, for whom the disease must be rapidly relieved. Further studies are warranted for exploring the advantageous patients with the receipt of bevacizumab in multiline treatment.

Vascular endothelial growth factor-A is an Immunohistochemical biomarker for the efficacy of bevacizumab-containing chemotherapy for duodenal and jejunal adenocarcinoma

BackgroundThe efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA.MethodsThis multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor-A (VEGF-A), TP53, Ki67, β-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins.ResultsA total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30–0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression.ConclusionImmunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.

The efficacy and safety profile of 2-weekly dosing of bevacizumab-containing chemotherapy for platinum-resistant recurrent ovarian cancer

BackgroundDespite being widely used, to date (June 2021), the regimen of bevacizumab 10 mg/kg every 2 weeks (Q2W) combined with chemotherapy is not approved in Japan for patients with platinum-resistant recurrent ovarian cancer. In this retrospective analysis, we evaluated the usage patterns of bevacizumab administered for platinum-resistant recurrent ovarian cancer.MethodsWe obtained clinical data from 155 Japanese medical facilities between November 2013 and December 2018 via a survey. Items included the number of cases of platinum-resistant recurrent ovarian cancer treated with bevacizumab according to dosage. For regimens including bevacizumab 10 mg/kg Q2W, additional information was requested relating to concomitantly administered agents, and the efficacy and safety of the regimen.ResultsOf 1739 bevacizumab-containing regimens reported in 1633 patients with recurrent ovarian cancer, 264 used 10 mg/kg Q2W. The overall response rate (ORR) with this regimen was 26.1%. Response rates varied according to regimen and were particularly favorable when bevacizumab 10 mg/kg Q2W was administered with paclitaxel (ORR, 53.0%) versus liposomal doxorubicin (15.0%; P < 0.0001) and irinotecan (7.7%; P < 0.028). The most frequent Grade ≥ 3 adverse events associated with bevacizumab 10 mg/kg Q2W were neutropenia (11.7%) and hypertension (11.7%). The most frequent bevacizumab-associated Grade ≥ 3 adverse events with bevacizumab plus paclitaxel versus bevacizumab plus liposomal doxorubicin were hypertension (9.0% versus 13.9%) and proteinuria (3.0% versus 8.4%).ConclusionsBevacizumab 10 mg/kg Q2W appears efficacious for patients with recurrent ovarian cancer, with a manageable toxicity profile. Approval of this regimen is clinically desirable for Japanese patients with ovarian cancer.

Radiomics diagnosed histopathological growth pattern in prediction of response and 1-year progression free survival for colorectal liver metastases patients treated with bevacizumab containing chemotherapy

ObjectiveTo investigate the capability of a radiomics model, which was designed to identify histopathologic growth pattern (HGP) of colorectal liver metastases (CRLMs) based on contrast-enhanced multidetector computed tomography (ceMDCT), to predict early response and 1-year progression free survival (PFS) in patients treated with bevacizumab-containing chemotherapy. MethodsPatients with unresectable CRLMs who were treated with bevacizumab-containing chemotherapy were included in this multicenter retrospective study. For each target lesion, the radiomics-diagnosed HGP (RAD_HGP) of desmoplastic (D) pattern or replacement (R) pattern was determined. Logistic regression and receiver operating characteristic (ROC) curves were used to assess lesion- and patient-based responses according to morphologic response criteria. One-year PFS was calculated using Kaplan-Meier curves. Hazard ratios for 1-year PFS were obtained through Cox proportional hazard regression analysis. ResultsAmong 119 study patients, 206 D pattern and 140 R pattern lesions were identified. In patients with multiple lesions, 52 had D pattern, 31 had R pattern, and 36 had mixed (D + R) pattern. The area under the curve value for RAD_HGP in predicting early response was 0.707 for lesion-based analysis and 0.720 for patient-based analysis. Patients with D pattern had a significantly longer PFS than patients with R pattern or mixed pattern (P < 0.001). RAD_HGP was the only independent predictor of 1-year PFS. ConclusionsHGP diagnosed using a radiomics model could be used as an effective predictor of PFS for patients with CRLMs treated with bevacizumab-containing chemotherapy.

Lactate Dehydrogenase Is a Useful Marker for Predicting the Efficacy of Bevacizumab-containing Chemotherapy in Patients With Metastatic Colorectal Cancer.

No biomarkers that predict the benefit from anti-vascular endothelial growth factor (VEGF) antibodies have been identified. It is necessary to discover biomarkers that can identify patients who are more likely to benefit from bevacizumab-containing treatment, especially those who are more likely to benefit from treatment with bevacizumab beyond progression (BBP). Levels of serum lactate dehydrogenase (LDH), reported to be an indirect marker of hypoxia and angiogenesis, may be a useful marker for monitoring the efficacy of suppression of angiogenesis. The clinical data of 91 patients with unresectable metastatic colorectal cancer who were treated with bevacizumab-containing chemotherapy as first-line treatment were collected and studied. In the second-line treatment, the bevacizumab plus chemotherapy group showed significantly better progression-free survival (PFS) in comparison to the chemotherapy-alone group in patients with low post-first-line-treatment serum LDH levels. On the other hand, no significant differences in the PFS rate were observed between the two groups in patients with high post-first-line-treatment serum LDH levels. The post-first-line-treatment serum LDH levels may, therefore, be useful marker for predicting the efficacy of treatment with BBP.

Identifying response in colorectal liver metastases treated with bevacizumab: development of RECIST by combining contrast-enhanced and diffusion-weighted MRI.

Response evaluation criteria in solid tumors (RECIST) often fail to identify clinically meaningful response to bevacizumab-containing therapy in colorectal liver metastasis (CRLM). This study aimed to develop RECIST by combining contrast-enhanced and diffusion-weighted magnetic resonance imaging (MRI). A total of 126 patients with CRLM who underwent hepatic resection after bevacizumab-containing chemotherapy were split into initial analyses cohort (N = 42, with 76 indexed liver metastases) and validation cohort (N = 84). In lesion-based analyses, percentage decrease of arterial enhancement area and percentage increase of apparent diffusion coefficient (ADC) value from baseline to post-chemotherapy were measured. Their optimal cutoff values for distinguishing pathology-confirmed major and minor response were determined. Then, the developed RECIST (D-RECIST) was established by combining functional and size-based items. Survival relevance of D-RECIST and RECIST was examined in the validation cohort. Percentage decrease of arterial enhancement area and increase of ADC value significantly differed between lesions of pathologic major or minor response, with optimal cutoffs of approximately 33% and 19%, respectively. Patients defined as responders by D-RECIST had a significantly longer median disease-free survival (DFS) than non-responders (p = 0.021; 12.9 versus 8.6 months). No significant difference was observed with RECIST (p = 0.524). In a Cox regression model, D-RECIST- but not RECIST-defined responses independently predicted the DFS (p = 0.034 and 0.811). D-RECIST-defined responses provided significant prognostic information, and thus may serve as a better response evaluation approach than RECIST in CRLM treated with bevacizumab-containing therapy. • Changes in arterial enhancement area and apparent diffusion coefficient value are associated with pathological response in colorectal liver metastases treated with bevacizumab. • The MRI-based response criteria developed by combining size-based and functional features can provide significant prognostic information.

Bevacizumab-associated events in Japanese women with cervical cancer: a multi-institutional survey of Obstetrical Gynecological Society of Kinki district, Japan.

The development of perforations or fistulas in the Gastrointestinal (GI) tract or genitourinary (GU) system is a serious adverse effect of bevacizumab. The aim of this study was to investigate the incidences of these GI/GU events as well as their association with previous radiotherapy (RT) in Japanese women with cervical cancer. We conducted a written questionnaire survey among 14 gynecological institutions belonging to the Oncology Research Committee of the Obstetrical and Gynecological Society of Kinki District, Japan. The severity of GI/GU events was classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0. All data were extracted from survey responses and maintained in an Excel spreadsheet and summarized using descriptive statistics. The information of 224 Japanese women with cervical cancer (152 recurrent and 72 advanced) who were treated with bevacizumab-containing chemotherapy was collected from 14 institutions. Of these, 65% had been previously treated with RT. GI/GU events of any grade developed in 25 (11.2%) patients, leading directly to death in 3 (1.3%) patients. When compared, the incidence of GI/GU events was higher in recurrent disease patients than in advanced disease patients (13.8% vs 5.6%, p = 0.0728). When examined according to the history of RT, the incidence of GI/GU events was greater in patients with a history of RT than in those without (14.5% vs 5.1%, p = 0.044). More than 10% of patients experience GI/GU events during or after receiving bevacizumab-containing chemotherapies. Prior RT is a risk factor for bevacizumab-associated GI/GU events.

Investigation of morphological and functional changes in the liver and pancreas during bevacizumab treatment

Objectives: Recently, there have been reports regarding the atrophy of various organs caused by molecular targeted drugs. We investigated morphological and clinical changes in the liver and pancreas caused by treatment with bevacizumab.Methods: We investigated 30 patients with colorectal cancer who received bevacizumab-containing chemotherapy (study group) and 11 patients with colorectal cancer who received chemotherapy without bevacizumab (control group) from 2010 to 2014. We obtained computed tomography data of the liver and pancreas and performed three-dimensional image analysis and volumetry. Laboratory data before and after chemotherapy were analyzed.Results: There was no significant difference in liver volume before and after bevacizumab-containing chemotherapy, but the pancreatic volume was found to be significantly reduced after bevacizumab-containing chemotherapy (57.9 ± 16 mL versus 47.4 ± 15.3 mL; p = .005). The liver and pancreatic volume did not change statistically in the control group. With regard to complete blood cell counts and laboratory data, no significant differences were observed in the leukocyte count and hemoglobin, hemoglobin A1c, triglyceride, albumin, and C-reactive protein levels. In contrast, there was a significant decrease in the platelet count, total cholesterol level and a significant increase in the amylase level. A chemotherapy regimen that included bevacizumab reduced pancreatic volume and significantly altered the morphology of the pancreas.Conclusions: Although bevacizumab caused atrophy of the pancreas and reduced pancreatic volume, pancreatic endocrine function showed no change. Future studies should investigate the survival rate and functional changes caused by bevacizumab treatment.

Efficacy of bevacizumab-containing chemotherapy in metastatic colorectal cancer and CXCL5 expression: Six case reports.

BACKGROUNDIn metastatic colorectal cancer (mCRC), the anti-vascular endothelial growth factor drug bevacizumab (BVZ) plus chemotherapy significantly improves progression-free survival compared to chemotherapy (CT) alone. This benefit is not, however, observed in all patients. While increased chemokine CXCL5 gene expression promoting angiogenesis has been proposed as a prognostic mCRC biomarker, few studies have examined its relationship with drug efficacy. This study sought to analyze tumor CXCL5 gene expression in six patients with different efficacy of BVZ-containing CT in terms of the tumor response to treatment.CASE SUMMARYWe report six cases of stage IV KRAS-mutated mCRC. Patients were given first line treatment with BVZ-containing chemotherapy in University Hospital of Fuenlabrada. The six patients differed in terms of primary tumor location (right/left side), tumor burden (mostly hepatic and peritoneal disease) and clinical disease course. Before treatment onset, total RNA was isolated from paraffinated tumor biopsy specimens and CXCL5 gene expression quantified through conventional RT-qPCR procedures. Our main finding was that CXCL5 expression levels were several times higher in three patients with lower progression free survival (under 6 mo) from the start of treatment.CONCLUSIONA higher expression of CXCL5 was observed in the three patients showing worse tumor response to treatment.

Signal changes in T2-weighted MRI of liver metastases under bevacizumab-A practical imaging biomarker?

The purpose of this study was to investigate signal changes in T2-weighted magnetic resonance imaging of liver metastases under treatment with and without bevacizumab-containing chemotherapy and to compare these signal changes to tumor contrast enhancement. Retrospective analysis of 44 patients, aged 36-84 years, who underwent liver magnetic resonance imaging including T2-weighted and dynamic contrast enhancement sequences. Patients received bevacizumab-containing (n = 22) or conventional cytotoxic chemotherapy (n = 22). Magnetic resonance imaging was obtained at baseline and at three follow-ups (on average 3, 6 and 9 months after initial treatment). Three independent readers rated the T2 signal intensity and the relative contrast enhancement of the metastases on a 5-point scale. T2 signal intensity of metastases treated with bevacizumab showed a significant (p<0.001) decrease in T2 signal intensity after initial treatment and exhibit compared to conventionally treated metastases significantly (p<0.001 for each follow-up) hypointense (bevacizumab: 0.70 ± 0.83 before vs. -1.55 ± 0.61, -1.91 ± 0.62, and -1.97 ± 0.52; cytotoxic: 0.73 ± 0.79 before vs. -0.69 ± 0.81, -0.71 ± 0.68, and -0.75 ± 0.65 after 3, 6, and 9 months, respectively). T2 signal intensity was strongly correlated with tumor contrast enhancement (r = 0.71; p<0.001). Intra-observer agreement for T2-signal intensity was substantial (κ = 0.75). The agreement for tumoral contrast enhancement between the readers was considerably lower (κ = 0.39). Liver metastases exhibit considerably hypointense in T2-weighted imaging after treatment with bevacizumab, in contrast to conventionally treated liver metastases. Therefore, T2-weighted imaging seems to reflect the effect of bevacizumab.