Bevacizumab Therapy In Patients Research Articles

Safety evaluation of lenvatinib treatment after atezolizumab plus bevacizumab therapy for patients with unresectable liver cancer: A comparison of lenvatinib as 1st‑ or 2nd‑line treatment.

Atezolizumab plus bevacizumab (Atez/BV) as first-line therapy and lenvatinib (LEN) as second-line therapy are the recommended treatments for patients with unresectable hepatocellular carcinoma. Adverse immune events caused by immune checkpoint inhibitors (such as Atez) generally only occur several months after administration; therefore, the potential influence of the first-line treatment on second-line treatment is not clear. The present study investigated the safety of second-line LEN treatment (2nd LEN) by comparing the adverse events (AEs) of 2nd LEN after first-line Atez/BV treatment for unresectable liver cancer, with those of first-line LEN treatment (1st LEN). Patients who received Atez/BV as first-line therapy and 2nd LEN, or those who received 1st LEN at Ogaki Municipal Hospital (Ogaki, Japan) between April 2018 and September 2023 were retrospectively evaluated for treatment duration and AEs. The median treatment duration for patients in the 1st LEN (n=39) and 2nd LEN (n=13) groups was 151.0 days [95% confidence interval (CI) 77-303 days] and 128.5 days (95% CI 68-270 days), respectively (P=0.385). A greater proportion of patients showed elevated aspartate aminotransferase/alanine aminotransferase levels in the 2nd LEN group (76.9%) compared with those in the 1st LEN group (46.2%) (P=0.016). Hypothyroidism was more common in those receiving 2nd LEN (46.2%) than 1st LEN (12.8%) (P=0.016). In addition, grade 1 (three patients) and grade 2 (three patients) hypothyroidism was observed in patients receiving 2nd LEN. For these six patients, during first-line Atez/BV treatment, four patients had grade 0 hypothyroidism and two patients had grade 1 hypothyroidism (P=0.025). In conclusion, patients receiving 2nd LEN after treatment with Atez/BV are at an increased risk of hypothyroidism.

Machine learning application identifies plasma markers for proteinuria in metastatic colorectal cancer patients treated with Bevacizumab.

Proteinuria is a common complication after the application of bevacizumab therapy in patients with metastatic colorectal cancer, and severe proteinuria can lead to discontinuation of the drug. There is a lack of sophisticated means to predict bevacizumab-induced proteinuria, so the present study aims to predict bevacizumab-induced proteinuria using peripheral venous blood samples. A total of 122 subjects were enrolled and underwent pre-treatment plasma markers, and we followed them for six months with proteinuria as the endpoint event. We then analyzed the clinical features and plasma markers for grade ≥ 2 proteinuria occurrence using machine learning to construct a model with predictive utility. One hundred sixteen subjects were included in the statistical analysis. We found that high baseline systolic blood pressure, low baseline HGF, high baseline ET1, high baseline MMP2, and high baseline ACE1 were risk factors for the development of grade ≥ 2 proteinuria in patients with metastatic colorectal cancer who received bevacizumab. Then, we constructed a support vector machine model with a sensitivity of 0.889, a specificity of 0.918, a precision of 0.615, and an F1 score of 0.727. We constructed a machine learning model for predicting grade ≥ 2 bevacizumab-induced proteinuria, which may provide proteinuria risk assessment for applying bevacizumab in patients with metastatic colorectal cancer.

Pretreatment eosinophil count predicts response to atezolizumab plus bevacizumab therapy in patients with hepatocellular carcinoma.

Pretreatment peripheral blood markers have value in predicting the treatment outcome of various cancers. In particular, the eosinophil count has recently gained attention. However, no study has reported the influence of the pretreatment eosinophil count on the outcomes of atezolizumab plus bevacizumab (ATZ/BEV), which is the recommended first-line systemic therapy for unresectable hepatocellular carcinoma (u-HCC). We enrolled 114 patients with u-HCC treated with ATZ/BEV (n=48) or lenvatinib (n=66). The patients receiving ATZ/BEV or lenvatinib were divided into two groups by calculating the cutoff value of the pretreatment eosinophil count. The groups were compared regarding the clinicopathological characteristics, outcomes, and incidence of adverse events (AEs). Twenty-three of 48 patients (47.9%) who received ATZ/BEV therapy were categorized as the ATZ/BEV-eosinophil-high group, which had better responses than the ATZ/BEV-eosinophil-low group (P=0.0090). Kaplan-Meier curves revealed a trend toward significantly better progression-free survival (PFS) in the ATZ/BEV-eosinophil-high group than the ATZ/BEV-eosinophil-low group (the median PFS: 4.7months in the ATZ/BEV-eosinophil-low group vs 12.6months in the ATZ/BEV-eosinophil-high group; P=0.0064). Multivariate analysis showed that a low eosinophil count was an independent risk factor for worse PFS after ATZ/BEV therapy (P=0.0424, hazard ratio: 2.24, 95% confidence interval: 1.02-4.89). AEs (≥ grade 3) were significantly more likely to occur in the ATZ/BEV-eosinophil-high group (P=0.0285). The outcomes did not significantly differ between the LEN-eosinophil-high group and the LEN-eosinophil-low group. A high pretreatment eosinophil count predicted a better response to ATZ/BEV therapy for u-HCC and was associated with the incidence of AEs (≥ grade 3).

The prediction of early progressive disease in patients with hepatocellular carcinoma receiving atezolizumab plus bevacizumab.

The IMbrave 150 trial revealed the usefulness of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (HCC), making it now considered the first-line systemic chemotherapy agent for HCC. The present study investigated factors associated with early tumor progression of atezolizumab plus bevacizumab in patients with advanced HCC in real-world clinical practice. A total of 184 HCC patients who received atezolizumab plus bevacizumab therapy were studied. We investigated the frequency of early progressive disease (e-PD; PD within 9 weeks) and analyzed the risk factors for e-PD. There were 47 patients (25.5%) diagnosed as e-PD. Patients with e-PD had a worse performance status (PS) and albumin-bilirubin (ALBI) and Child-Pugh (C-P) scores and a significantly higher rate of a systemic therapy than those with non-e-PD. A multivariate analysis showed that PS ≥1 (odds ratio [OR] = 4.5, 95% confidence interval [CI] = 1.9-10, p < 0.001), ALBI score ≥-2.30 (OR = 2.1, 95% CI = 1.0-4.5, p = 0.044) and the history of a systemic therapy (OR = 3.0, 95% CI = 1.4-6.4, p = 0.0038) were significant and independent determinants of e-PD. When examining the liver function trends in e-PD patients, the ALBI scores at 3 and 6 weeks after starting therapy were significantly higher than before the treatment (p < 0.001). The liver function and systemic therapy are useful predictors of e-PD in HCC patients treated with atezolizumab plus bevacizumab in real-world clinical practice.

An open-label, multicenter study investigating RP3 oncolytic immunotherapy in combination with first- or second-line systemic atezolizumab and bevacizumab therapy in patients with locally advanced unresectable or metastatic hepatocellular carcinoma.

TPS4178 Background: Despite advances in treatment for unresectable hepatocellular carcinoma (HCC), long-term survival rates remain poor. The combination of bevacizumab (Bev) and atezolizumab (Atezo) is the preferred frontline therapy for advanced HCC, but a minority of patients (pts) respond, and secondary resistance usually occurs within months. HCC has an immune-suppressed tumor microenvironment, mediated by activated immune checkpoint signaling and angiogenesis pathways, which may contribute to therapeutic resistance. RP3 is a genetically modified herpes simplex virus type 1 (HSV-1) that expresses the fusogenic gibbon ape leukemia virus glycoprotein with the R sequence deleted (GALV-GP-R–), an anti–CTLA-4 antibody-like molecule, CD40 ligand, and 4-1BB ligand. The direct oncolytic effect coupled with immune stimulation by RP3 in the tumor microenvironment is intended to provide systemic antitumor activity and enhance therapeutic response to anti–PD-1/PD-L1 agents, such as Atezo. Preclinical data have demonstrated improved distribution of oncolytic HSV within tumors in combination with Bev, supporting the clinical combination of RP3 with Bev. This study will evaluate the safety and efficacy of RP3 combined with Atezo and Bev as first- (1L) and second-line (2L) systemic therapies for unresectable and advanced HCC. Methods: The 1L and 2L cohorts will each enroll up to 30 pts. Pts in the 1L cohort may not have received prior systemic treatment; pts in the 2L cohort must have progressed on or following one prior line of systemic therapy, which must have included a PD-1/PD-L1−directed agent. Key inclusion criteria include advanced, unresectable HCC with ≥1 measurable tumor of ≥1 cm in longest diameter, Child-Pugh Class A, and Eastern Cooperative Oncology Group performance status of 0−1. Key exclusion criteria include untreated esophageal and/or gastric varices with bleeding or at high risk for bleeding and macroscopic invasion of tumor into any major blood vessel(s) and/or main bile ducts. Pts with a history of medically refractory hepatic encephalopathy and/or hepato-renal syndrome are also excluded. Pts in the 1L cohort will receive 1200 mg Atezo and 15 mg/kg Bev every 3 weeks (Q3W) together with RP3 intratumorally Q3W for a total of up to 8 doses. Pts in the 2L cohort will receive RP3 every 2 weeks for 4 doses with Bev Q3W starting on cycle (C) 1 day (D) 1, then RP3 and Bev Q3W for up to 4 more doses with Atezo Q3W being added on C4D1. The primary endpoint is overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints are safety, ORR using HCC modified RECIST, duration of response, complete response rate, and progression-free survival. Clinical trial information: NCT05733598 .

Abstract P5-02-48: Identifying immune-related predictive factors for paclitaxel + bevacizumab therapy in patients with HER2-negative advanced breast cancer- A multicenter retrospective study

Abstract Background: In IMpassion 130 trial, programmed death-ligand 1 (PD-L1) expression was seen in about 40% of participated patients with triple negative advanced breast cancer (TN-ABC) [Schmid, 2018, N Engl J Med], however, actual situation of PD-L1 expression in patients HER2-negative ABC patients including with TN-ABC has not been well studied. Furthermore, no biomarker related to chemotherapy for HER2-negative ABC patients except for PD-L1 in TN-ABC has been identified. Recently, several reports regarding the relationship between peripheral immune-related markers; such as absolute lymphocyte count (ALC) or neutrophil-to-lymphocyte ratio (NLR), and efficacy of eribulin therapy [Miyoshi, 2020, Breast Cancer; Watanabe, 2020, Breast Cancer Res Treat] or paclitaxel plus bevacizumab (PB) therapy [Nakamoto, 2021, Sci Rep], however, the relationship between the efficacy of PB therapy and peripheral immune related markers including dynamic change during the therapy or local immune-related markers is unclear. Therefore, we conducted multi-institutional, retrospective study 1) to evaluate the actual situation of PD-L1 expression and other immune-related markers of the primary site by central review, and 2) to explore biomarkers for first-line PB therapy using peripheral and local immune-related markers. Patients and methods: We retrospectively reviewed medical records of HER2-negative ABC patients who received PB therapy as first-line (1L) or second-line chemotherapy for ABC. Clinical data including ALC, NLR and serum albumin (Alb) were extracted from medical records, and the pathology of archived tissues of primary and metastatic site (if available) were centrally reviewed including PD-L1 (VentanaR SP142). Statistical analyses were performed using Kaplan-Meier method, log-rank test, Wilcoxon’s test, and Cox hazard model. Mixed-effects model for repeated measures (MMRM) to evaluate the relationships between dynamic change in immune-related markers and time-to treatment termination (TTT) of PB therapy. Results: We identified 156 HER2-negaive ABC patients who underwent PB therapy, and 114 out of 156 patients were eligible for analyses. Of 114 patients, 63 patients (55.3%) had recurrent disease, and 65 (57.0%) patients had visceral disease. Eighty-seven out of 114 (76.3%) patients received PB therapy as 1L chemotherapy. Eighty-four specimens (73.7%) were diagnosed as estrogen-receptor (ER) positive, and PD-L1 positivity rate were 3.6% (1/84) in ER+ subgroup and 30.0% (6/20) in ER- subgroup, respectively. Paired biopsy specimens were eligible in 14 patients, and significant elevation of Ki67 labeling index was noted. In patients who received 1L PB (n = 87), there was no positive relationship between maintained ALC (&amp;gt;1,500 or &amp;gt;1,000/μL at baseline) or low NLR (&amp;lt; 2.5 or &amp;lt; 3) at the initiation of 1L PB therapy and TTTs. However, low NLR (cut-off at 2.5 and 3) at the initiation of second cycle of PB therapy reduced the risk for treatment-termination as; hazard ratio [HR], 0.427; 95% CI 0.218-0.843; P = 0.0147 and HR, 0.344; 95% CI 0.170-0.731; P = 0.0066, respectively. PD-L1 positive patients (n = 5) showed numerically increased risk of treatment-termination (HR, 2.68; 95% CI, 0.922-6.196; P = 0.0674) for 1L PB therapy, however, there was no significant difference in mortality risk regarding PD-L1 statuses. Multivariate analysis using MMRM disclosed that increase of Alb level was predictive factor for 1L PB therapy (HR, 0.41; 95%CI, 0.18-0.93; P = 0.0338). Conclusion: According to our real-world study, 1) PD-L1 positive rate was lower than that of previous reports, 2) low NLR at the initiation of second cycle of PB therapy and dynamic change in albumin level were identified as predictive factors and 3) PD-L1 overexpression was not a prognostic or a predictive factor for PB therapy in patients with HER2-negative ABC. Funding: Chugai Pharmaceutical CO., LTD. Citation Format: Junichiro Watanabe, Takashi Sugino, Koji Muramatsu, Satoshi Morita, Yu Hidaka, Shogo Nakamoto, Mitsuya Ito, Shoichiro Ohtani, Masahiko Ikeda. Identifying immune-related predictive factors for paclitaxel + bevacizumab therapy in patients with HER2-negative advanced breast cancer- A multicenter retrospective study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-48.

An open-label, multicenter study investigating RP3 oncolytic immunotherapy in combination with first- or second-line systemic atezolizumab and bevacizumab therapy in patients with locally advanced unresectable or metastatic hepatocellular carcinoma.

TPS623 Background: Despite advances in treatment for unresectable hepatocellular carcinoma (HCC), long-term survival rates remain poor. The combination of bevacizumab (Bev) and atezolizumab (Atezo) is the preferred frontline therapy for advanced HCC, but a minority of patients (pts) respond, and secondary resistance usually occurs within months. HCC has an immune-suppressed tumor microenvironment, mediated by activated immune checkpoint signaling and angiogenesis pathways, which may contribute to therapeutic resistance. RP3 is a genetically modified herpes simplex virus 1 (HSV-1) that expresses the fusogenic GALV-GP R- protein, an anti–CTLA-4 antibody-like molecule, CD40 ligand, and 4-1BB ligand. The direct oncolytic effect coupled with immune stimulation by RP3 in the tumor microenvironment is intended to provide systemic anti-tumor activity and reverse therapeutic resistance to anti-PD-1/PD-L1 agents. Pre-clinical data has demonstrated improved distribution of oncolytic HSV within tumors in combination with Bev supporting the clinical combination of RP3 with Bev. RP3 combined with anti-PD1 therapy has demonstrated clinical activity and safety in pts with various malignant solid tumors. This study will evaluate the safety and efficacy of RP3 combined with Atezo and Bev as 1st (1L) and 2nd (2L) line systemic therapies for inoperable and advanced HCC. Methods: The 1L and 2L cohorts will each enroll up to 30 pts with advanced, unresectable HCC. Pts in the 1L cohort may not have received prior systemic treatment; pts in the 2L cohort must have progressed on or following one prior line of systemic therapy, which must have included a PD-(L)1 directed agent. Key inclusion criteria include advanced unresectable HCC with at least 1 measurable tumor of ≥1 cm in longest diameter, Childs-Pugh Class A, and ECOG Score of 0 or 1. Important exclusion criteria include untreated esophageal and/or gastric varices with bleeding or at high risk for bleeding, and macroscopic invasion of tumor into major blood vessels and/or main bile ducts. Pts with a history of medically refractory hepatic encephalopathy and/or hepato-renal syndrome are also excluded. Pts in 1L cohort will receive 1200 mg Atezo and 15mg/kg Bev Q3W together with RP3 intratumorally (IT) Q3W for a total of up to 8 doses. In 2L pts will receive RP3 Q2W for 4 doses with Bev Q3W starting on C1D1, then RP3 and Bev Q3W for up to 4 more doses with Atezo Q3W being added on C4D1. The primary endpoint includes overall response rate (ORR) by RECIST v1.1. Secondary endpoints are safety, ORR using HCC mRECIST, duration of response, complete response rate, and progression-free survival.

The benefit of bevacizumab therapy in patients with refractory vasogenic edema caused by brain metastasis from lung and colon cancers.

ObjectiveThis retrospective study investigated the efficacy of bevacizumab in refractory brain edema caused by brain metastasis from lung cancer and colon cancer.MethodsA total of 72 patients with refractory brain edema were divided into the lung cancer and colon cancer groups according to their primary tumor. All patients received a single bevacizumab treatment for refractory brain edema. MRI was performed 1 week before the treatment and 4 weeks after the treatment. The edema and tumor volumes were calculated using imaging modalities.ResultsAfter a single bevacizumab treatment, the refractory brain edema of 61 patients was controlled, and the clinical symptoms of 65 patients were improved. The average edema volume before treatment was 201,708.97 ± 61,426.04 mm3, which has decreased to 116,947.01 ± 43,879.16 mm3 after treatment (P < 0.05). After treatment, the edema index decreased from 25.97 ± 7.15 to 17.32 ± 5.24 (P < 0.05).We found that brain edema was controlled in 40 patients (93.02%) in the lung cancer group and 21 patients (72.41%) in the colon cancer group (P<0.05). In addition, 22 patients (88.00%) in the radiotherapy group achieved edema control, compared to 39 (82.98%) in the non-radiotherapy group (P>0.05). Nine patients experienced hypertension after treatment, two patients exhibited decreased platelet counts, and no hemorrhage cases were observed.ConclusionBevacizumab can significantly alleviate refractory brain edema, and there is a significant difference in the efficacy of bevacizumab on refractory brain edema caused by brain metastasis from lung and colon cancers.

Adverse Events Associated With Long-term Treatment of Epithelial Ovarian Cancer With Bevacizumab and Chemotherapy.

Adverse events associated with long-term bevacizumab administration for ovarian cancer have been poorly documented in Japan. This study aimed to evaluate the adverse events of bevacizumab combined with chemotherapy for treating primary and recurrent epithelial ovarian cancer in Japan. In this single-center retrospective study, we analyzed data of patients with advanced and recurrent epithelial ovarian cancer treated with bevacizumab and chemotherapy between January 2013 and November 2019. Statistical analyses were performed using the Fisher's exact test and Kaplan-Meier method. A total of 46 patients were included and the follow-up time was 30 months. The median duration of bevacizumab treatment was 14 months, and the median total dose of bevacizumab was 247.5 mg/kg. The most common adverse events were hypertension (n=30; 65.2%) and proteinuria (n=24; 49%) in all grades. The onset of hypertension and proteinuria occurred at a median of 2 months and 14 months after treatment initiation in all grades, respectively. Gastrointestinal perforation occurred significantly more frequently in patients with a history of radiation therapy. This study included cases of primary advanced and recurrent epithelial ovarian cancer, and had a longer observation period and reported more adverse events of bevacizumab with chemotherapy than previous reports. The administration of bevacizumab therapy in patients with a history of radiation should be carefully considered due to increased chances of gastrointestinal perforation.

Clinical Usefulness of Monitoring Muscle Volume during Atezolizumab Plus Bevacizumab Therapy in Patients with Unresectable Hepatocellular Carcinoma.

Simple SummaryDecrease of skeletal muscle mass index during atezolizumab plus bevacizumab therapy was significantly associated with poor progression-free survival in patients with unresectable hepatocellular carcinoma, while pretreatment sarcopenia was not a significant factor. These findings suggest that monitoring skeletal muscle volume during immunotherapy may be useful for predicting clinical outcomes.Background: Sarcopenia is associated with overall survival in patients with hepatocellular carcinoma (HCC). However, it is not known whether muscle volume is associated with clinical outcomes during combination therapy with immune checkpoint inhibitors. We investigated the relationship between changes in muscle volume and treatment outcomes in patients treated with atezolizumab plus bevacizumab. Methods: Thirty-two patients with HCC who received atezolizumab plus bevacizumab as the first-line treatment between October 2020 and February 2022 were included. Skeletal muscle mass index (SMI) was calculated from the skeletal muscle area at the L3 level of the lumbar vertebrae. We compared pretreatment SMI and SMI at 6–14 weeks after administration. Results: Of the 32 patients, 18 had a decreased SMI, while 14 did not. Progression-free survival (PFS) was significantly longer in patients without SMI decrease than in patients with SMI decrease (8.5 vs. 5.8 months, p = 0.011). There were no significant differences in treatment-related adverse events between the patients with and without SMI. Presarcopenia at baseline was not significantly associated with PFS. Conclusions: Decreased SMI was significantly associated with PFS. Monitoring muscle volume during atezolizumab plus bevacizumab therapy is useful in clinical practice.

Comparison between post treatment vascular density, fractal dimension and choriocapillaris flow in ischemic and non-ischemic retinal vein occlusion using optical coherence tomography angiography

The aim of the study was to compare vascular density (VD), fractal dimension (FD), foveal avascular zone (FAZ) and choriocapillaris flow and using optical coherence tomography angiography (OCTA) before and after Bevacizumab therapy in patients with macular edema associated with ischemic and non-ischemic retinal vein occlusion (RVO). 15 eyes with ischemic RVO and 20 with non-ischemic RVO were included. Each patient had 3 consecutive intravitreal injections of Bevacizumab every month. Best-corrected visual acuity (BCVA), central macular thickness (CMT) and retinal microvasculature were measured using OCTA before and one month after the third injection. The BCVA and FAZ area improved significantly after treatment in both ischemic and non-ischemic cases. Although, in ischemic group, FD, superficial and deep capillary VD decreased with no statistically significant change in the choriocapillaris flow. In the non-ischemic group, there was an increase in the FD, superficial parafoveal, perifoveal VD and choriocapillaris flow with insignificant increase in the DCP VD while the foveal VD showed a statistically significant decrease. In conclusion, anti-VEGF therapy improved the BCVA, retinal FD, VD in non-ischemic case but despite improvement in BCVA it reduced the VD in the ischemic cases.

Early experience of atezolizumab plus bevacizumab therapy in Japanese patients with unresectable hepatocellular carcinoma in real-world practice.

We aimed to investigate the efficacy and safety of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (u-HCC) based on whether they had previously received systemic therapy, as well as the association of atezolizumab plus bevacizumab with early alpha-fetoprotein (AFP) response in real-world practice. A total of 52 patients with u-HCC were treated with atezolizumab plus bevacizumab between October 2020 and April 2021. The Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST were used to evaluate radiological responses. The patients received atezolizumab plus bevacizumab as 1st-line (n = 23), 2nd-line (n = 16), 3rd-line (n = 6), 4th-line (n = 3), 5th-line (n = 3), or 6th-line (n = 1) therapy. According to RECIST, the objective response rate (ORR) and disease control rate (DCR) in all patients were 15.4% and 57.7%. In the 1st-line patients, ORR and DCR based on RECIST 1.1 were 27.3% and 81.8%. The median time to progression (TTP) assessed by RECIST was significantly longer among patients receiving atezolizumab plus bevacizumab as 1st-line therapy than in patients receiving atezolizumab plus bevacizumab as later-line therapy (P < 0.001). Patients with an AFP response (reduction ≥ 20% from baseline) at 6weeks had a significantly longer TTP assessed by RECIST than those without an AFP response (P = 0.02). Patients who received atezolizumab plus bevacizumab as 1st-line therapy had better clinical outcome than those who received atezolizumab plus bevacizumab in later lines. The AFP response at 6weeks could be a predictor of disease progression.

Effects of Intravitreal Bevacizumab Therapy in Patients with Proliferative Diabetic Retinopathy.

IntroductionDiabetes mellitus (DM) stands out as one of the chronic diseases with the highest morbidity and mortality rates worldwide. Among the many complications of DM, diabetic retinopathy (DR) is one of the causes of blindness in patients aged between 20 and 64 years. At least 90% of the new cases showed to have the retinal structure and function restored when proper treatment was provided.AimTo evaluate the efficacy of the antiangiogenic bevacizumab in the treatment of DR according not only to the clinical laboratory parameters for glycated hemoglobin (HbA1C) and capillary glycemia but also to the ophthalmological parameters for optical coherence tomography (OCT) and best-corrected visual acuity (BCVA).Patients and MethodsA total of 11 individuals were included and followed up for 12 months after 3 administrations of bevacizumab.ResultsUpon associating the ophthalmological and laboratory variables throughout the treatment, no significant alterations could be seen regarding the analyzed variables. However, it was observed that HbA1c values and the total leukocyte count negatively interfered with the treatment response.ConclusionThe current study showed that HbA1c values and the amount of leukocytes negatively interfere with the therapeutic response. Therefore, laboratory analyses of these parameters are recommended for diabetic patients undergoing the above-mentioned treatment.

P-347 A phase 3, randomized, double-blind, placebo-controlled study of transarterial chemoembolization combined with durvalumab or durvalumab plus bevacizumab therapy in patients with locoregional hepatocellular carcinoma: EMERALD-1

Patients with intermediate-stage hepatocellular carcinoma (HCC) are treated with locoregional therapy such as transarterial chemoembolization (TACE) because curative therapy is not always an option and there is no standard systemic therapy. TACE therapy achieves tumor responses, but progression and recurrence are common and often occur within 1 year. Early evidence shows encouraging activity and durable clinical response for checkpoint inhibitors (CIs), such as durvalumab, as treatment for advanced HCC (Kelley, et al.

Prospective Feasibility Study of Amrubicin and Bevacizumab Therapy for Patients With Previously Treated Advanced NSCLC.

The efficacy of the combination of amrubicin and bevacizumab against advanced non small-cell lung cancer (NSCLC), as a second or third-line treatment, was evaluated. Amrubicin was administered for 3 days to patients with previously treated advanced NSCLC, whereas bevacizumab was administered on day 1 of each cycle; this regimen was repeated every 3 weeks. Among the 16 patients, an overall response rate of 12.5% (for two patients) was achieved, and the overall disease control rate was 93.7%. Progression free survival and overall survival were 8.5 and 16.6 months, respectively. Grade 3 or 4 haematological toxicities were leukopenia, neutropenia, and febrile neutropenia. Grade 3 proteinuria and infection were the non haematological adverse events. The combination of amrubicin and bevacizumab is a promising regimen in the second or third-line treatment for advanced non-squamous NSCLC; however, physicians must recognise the risk of proteinuria related with this regimen.

511P - Phase II trial of carboplatin, nab-paclitaxel and bevacizumab for advanced non-squamous non-small cell lung cancer (CARNAVAL study; TORG1424/OLCSG1402)

BackgroundNanoparticle albumin-bound paclitaxel (nab-PTX) + carboplatin (Cb) therapy is one of the standard platinum-containing chemotherapy regimens for patients with advanced non-small cell lung cancer (NSCLC). Adding the anti-vascular endothelial growth factor antibody bevacizumab (BEV) to chemotherapy is an effective treatment option for non-squamous NSCLC. Because the efficacy and safety of the Cb + nab-PTX + BEV triplet regimen has not yet been assessed, we conducted a multicenter, open-label, phase I/II trial of Cb + nab-PTX + BEV therapy for patients with NSCLC. The phase II trial was based on the drug dose and schedule determined in the phase I trial. MethodsIn this phase II trial, the required number of patients was calculated to be 49 cases with α = 0.05 (one-sided) and β = 0.1 assuming a threshold response rate of 30% and an expected response rate of 50%. The patients were to receive 4–6 cycles of Cb (area under the curve = 6) + nab-PTX (100 mg/m2 on days 1, 8 and 15) + BEV (15 mg/kg on day 1) followed by a maintenance dose of nab-PTX + BEV every 3 weeks until disease progression. The primary endpoint was the overall response rate (ORR), and the secondary endpoints included overall survival (OS), progression free survival (PFS) time and toxicity. ResultsThe trial was terminated early because of slow patient accrual. Finally, 47 cases were registered, and the main analysis was performed in 46 cases, excluding one case who was unqualified. The median age of the patients was 66 years. The transition percentage to maintenance therapy was 58.7%. The ORR based on central judgment was 56.5% (26/46 cases) with a 95% confidence interval (CI) of 42.2–70.8%, and the primary endpoint was met. The median PFS and OS were 7.79 months and 18.9 months, respectively. The main toxicity was myelosuppression, with grade 3–4 neutropenia (72.0%), anemia (28.0%), thrombocytopenia (14.0%) and febrile neutropenia (2.0%). The grade 3–4 sensory and motor neuropathy commonly seen with paclitaxel was 0%. All adverse events were manageable, and there was no treatment-related death. ConclusionsCb + nab-PTX + BEV therapy is a favorable and well-tolerated treatment for patients with advanced non-squamous NSCLC. Clinical trial identificationUMIN000014560. Legal entity responsible for the studyTORG/OLCSG. FundingTaiho Pharmaceutical CO., LTD. DisclosureT. Kubo: Honoraria (self): Taiho pharmaceutical; Honoraria (self): Chugai pharmaceutical; Honoraria (self): BMS. A. Bessho: Honoraria (self): Taiho pharmaceutical; Honoraria (self): Chugai pharmaceutical. A. Morita: Honoraria (self): Chugai pharmaceutical. T. Yokoyama: Honoraria (self): Taiho pharmaceutical; Honoraria (self): Chugai pharmaceutical. K. Kaira: Honoraria (self): Taiho pharmaceutical; Honoraria (self): BMS. T. Harada: Honoraria (self): Taiho pharmaceutical. T. Shimokawa: Research grant / Funding (institution): Taiho pharmaceutical; Research grant / Funding (institution): Chugai pharmaceutical; Research grant / Funding (institution): BMS. K. Kiura: Research grant / Funding (institution): Chugai pharmaceutical; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Taiho pharmaceutical. H. Okamoto: Research grant / Funding (institution): Taiho pharmaceutical; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Chugai pharmaceutical. All other authors have declared no conflicts of interest.

Safety and Oncological Outcomes of Bevacizumab Therapy in Patients With Advanced Colorectal Cancer and Self-expandable Metal Stents

BackgroundMalignant bowel obstruction can occur in 18% of cases. Self-expandable metal stents (SEMS) can be an alternative to surgery. Bevacizumab (BV) has been associated with bowel perforation, but data on the safety of SEMS for occlusive colon cancer during BV-containing regimens are lacking. Material and MethodsThis is a retrospective analysis of 78 patients with malignant bowel obstruction who underwent placement of SEMS as a palliative intent for stage IV disease. Chemotherapy and BV-containing regimens, stent-related complications, and outcomes were recorded. ResultsOverall, major stent-related complications were observed in 27 (35%) patients: Re-obstruction occurred in 14 (52%) patients, and there were 7 (26%) perforations, 4 (15%) minor bleeding, and 2 (7%) migrations. Sixteen patients received BV; 2 (12.5%) had a perforation. No differences were observed between chemotherapy alone and BV in overall complications. Univariate analysis did not show that BV was more likely to develop perforations, although the incidence was higher in this subset of patients. Kaplan-Meier analysis showed a significant association with longer overall survival for patients treated with systemic therapy (27 vs. 11 months; P ≤ .00001). Also, there is a significant benefit of BV compared with chemotherapy alone (43 vs. 39 months; P = .02). ConclusionPlacement of SEMS is effective and relatively safe but with an overall complication rate of 35% in the metastatic setting. The major early risk is perforation, which can increase up to 12% during BV treatment. In patients with obstructing advanced colorectal cancer that would benefit from SEMS, we should consider the risks associated with systemic therapies, taking into account the improvement in survival observed with BV.

Outcome of Bevacizumab Therapy in Patients with Recurrent Glioblastoma Treated with Angiotensin System Inhibitors

ABSTRACTPurpose: Antihypertensive therapy may improve bevacizumab efficacy in cancer patients. We examined efficacy and toxicity of angiotensin system inhibitors (ASI) and other antihypertensive drugs in bevacizumab treated recurrent glioblastoma patients.Methods: We retrospectively combined a national prescription registry with a clinical database with recurrent glioblastoma patients (n = 243).Results: Patients who initiated ASI after bevacizumab (n = 26) showed a tendency towards improved progression-free survival and overall survival (OS) with hazard rate (HR) reductions (HR = 0.70 and HR = 0.79, respectively). Calcium antagonists during bevacizumab therapy significantly improved OS (HR = 0.57).Conclusions: Overall the study supports a potential beneficial effect of antihypertensive treatment on prognosis of bevacizumab treated glioblastoma patients.

Iatrogenic pseudoaneurysm after bevacizumab therapy in patients with metastatic colorectal cancer: Two case reports.

Pseudoaneurysms are extremely rare in patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI and bevacizumab in the first-line setting. We herein present two rare cases of iatrogenic pseudoaneurysm developing in patients with mCRC after administration of FOLFIRI and bevacizumab. The first patient was a 57-year-old man who was admitted to our institution with intermittent massive bloody discharge following treatment with the 9th cycle of FOLFIRI combined with bevacizumab. Colonoscopic examination revealed sizeable bloody clots in the rectum, but no active bleeder was identified; however, the patient's hemoglobin level was found to be persistently decreased, so an angiography was performed. The angiography revealed a pseudoaneurysm with contrast extravasation from a branch of the left internal iliac artery. Embolization of the bleeding vessel was performed, and the post-embolization angiography revealed no active bleeding. The second patient was a 65-year-old man who observed blood in the stool following treatment with the 5th cycle of FOLFIRI combined with bevacizumab. The angiography revealed a pseudoaneurysm in the superior rectal artery, and intravascular embolization with coils was performed. The patient was discharged without any signs of recurrent bleeding. Following a review of the relevant English literature, to the best of our knowledge, this is the first report on the formation of a bevacizumab-related pseudoaneurysms in mCRC patients. The aim of this study was to alert clinicians to the possibility of this rare complication.

Predictive tools for bevacizumab therapy in patients with aggressive HER 2-negative metastatic breast cancer: 2-years results from an observational study.

12043Background: The determination of monitoring Circulating Tumor Cells (CTC) in patients (pts) with metastatic breast cancer (MBC) is a well-established prognostic marker of efficacy/tolerance. W...