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Safety and efficacy of FOLFOX plus bevacizumab or FOLFIRI plus bevacizumab as second line Therapy in Advanced colorectal Cancer previously treated with bevacizumab.

ABSTRACT: Interventions: FOLFOX plus bevacizumab or FOLFIRI plus bevacizumab is treated until progression. Primary outcome(s): progression free survival Study Design: Single arm Non-randomized

DISEASE(S): Advanced Colorectal Cancer

PROVIDER: 2617856 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Single-Cell Analysis Reveals Cellular Reprogramming in Advanced Colon Cancer Following FOLFOX-Bevacizumab Treatment

Project description:The combination of FOLFOX and bevacizumab (FOLFOX-Bev) is a promising treatment for advanced colorectal cancer (CRC). To gain insights into the cellular changes associated with FOLFOX-Bev treatment, we conducted single-cell transcriptomic analysis of CRC samples derived from a patient before and after treatment. Our results show that cancer cells with high proliferative, metastatic, and pro-angiogenic properties respond better to FOLFOX-Bev treatment. Moreover, FOLFOX-Bev enhances CD8+ T cell cytotoxicity, thereby boosting the anti-tumor immune response. Conversely, FOLFOX-Bev impairs the functionality of tumor-associated macrophages, plasma cells, and cancer-associated fibroblasts, leading to a decrease in VEGFB-mediated angiogenesis. Furthermore, FOLFOX-Bev treatment reset intercellular communication, which could potentially affect the function of non-cancer cells. Our findings provide valuable insights into the molecular mechanisms underlying the response of advanced CRC to FOLFOX-Bev treatment and highlight potential targets for improving the efficacy of this treatment strategy.

2023-07-20 | GSE232525 | GEO

Immuno-priming with bevacizumab: durvalumab plus bevacizumab after prolonged exposition to bevacizumab in breast cancer

Project description:Immuno-priming with bevacizumab: durvalumab plus bevacizumab after prolonged exposition to bevacizumab in breast cancer

| PRJNA578152 | ENA

Immuno-priming with bevacizumab: durvalumab plus bevacizumab after prolonged exposition to bevacizumab in breast cancer

Project description:Purpose: To study the potential priming benefit of bevacizumab from subsequent immunotherapy (durvalumab) in advanced breast cancer patients Methods: We tested this hypothesis by adding durvalumab after progression to maintenance single-agent bevacizumab treatment in advanced HER2-negative patients (average 3 treatment lines). In order to study the potential priming benefit, patients had to experience disease progression while on bevacizumab maintenance prior to entering the trial. In addition, we sought to find traits in peripheral-blood mononuclear cells (PBMCs) and tumor biopsies that informed about this immuno-priming, in an attempt to search for novel biomarkers of efficacy of the combo and obtain a better understanding of the biology of this clinical scenario. Results: Patients that experienced clinical benefit, compared with the remaining patients, displayed a lymphocyte pattern in PBMCs consisting on increased T-effector subpopulations (CD4- and CD8- effector and effector-memory) and decreased immunosuppressive T-regulatory cells. Gene-expression studies in tumor samples showed a congruent pattern, with increased T-effector and memory T cell signatures in responders, and increased T-regulatory and decreased active dendritic cells in non-responders. These events were observed in patients that displayed vascular normalization features as a result of previous bevacizumab, supporting the immuno-priming effects of this strategy.

2020-10-15 | GSE139050 | GEO

Randomized phase III study of FOLFOX plus bevacizumab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer

Project description:Interventions: FOLFOX plus bevacizumab FOLFIRI plus bevacizumab Primary outcome(s): Progression free survival Study Design: Parallel Randomized

| 2616888 | ecrin-mdr-crc

Real-time quantitative PCR analysis of U87ΔEGFR intracranial mouse models treated with bevacizumab

Project description:The combination of bevacizumab with temozolomide and radiotherapy was shown to prolong progression-free survival in newly diagnosed glioblastoma patients, and this emphasizes the potential of bevacizumab as a glioma treatment. However, while bevacizumab effectively inhibits angiogenesis, it has also been reported to induce invasive proliferation. This study examined gene expression in glioma cells to investigate the mechanisms of bevacizumab-induced invasion. We made a human glioma U87ΔEGFR cell xenograft model by stereotactically injecting glioma cells into the brain of animals. We administered bevacizumab intraperitoneally three times per week. At 18 days after tumor implantation, the brains were removed for histopathology and mRNA was extracted. In vivo, bevacizumab treatment increased glioma cell invasion. qRT-PCR array analysis were perfomed.

2019-02-07 | GSE126168 | GEO

TAS-102, Irinotecan, and Bevacizumab in Pre-treated Metastatic Colorectal Cancer (TABAsCO), A Phase II Clinical Trial. ClinicalTrials.gov NCT04109924

Project description:Background: The efficacy of FOLFIRI plus an antiangiogenesis biologic agent as 2nd line therapy for metastatic colorectal adenocarcinoma is limited. TAS-102 is a novel oral antimetabolite with a distinct mechanism of action from fluoropyrimidines. We evaluated the antitumor efficacy of TAS-102, irinotecan and bevacizumab in patients with pre-treated, advanced colorectal adenocarcinoma in a multicenter, phase II, single-arm study. Methods: Patients with advanced colorectal adenocarcinoma who had progressed after oxaliplatin and fluoropyrimidine and were eligible for treatment with bevacizumab were treated with irinotecan, bevacizumab, and TAS-102 in 28-day cycles. The primary endpoint was progression-free survival (PFS). Results: We enrolled 35 evaluable patients. The study was positive. The median PFS was 7.9 (90% CI 6.2-11.8) months (vs. 6 months in historical control, p=0.018). The median overall survival was 16.5 (90% CI 9.8-17.5) months. Sixty-seven percent of patients experienced grade 3 or higher treatment-related adverse events. The most common toxicities were hematological (neutropenia) and gastrointestinal (diarrhea, nausea, and vomiting). Conclusions: Irinotecan, TAS-102 and bevacizumab is an active 2nd line therapy for patients with metastatic colorectal adenocarcinoma. Neutropenia is common and can affect dose density/intensity mandating use of G-CSF. A randomized study versus standard of care therapy is warranted.

2024-08-26 | GSE275628 | GEO

Serial Changes of Circulating Tumor Cells in Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab

Project description:Background and aims: Immune checkpoint inhibitors have promising outcomes in patients with hepatocellular carcinoma (HCC); however, there is no reliable biomarker for predicting disease progression. Circulating tumor cells (CTCs) derived from peripheral blood have attracted attention in monitoring therapeutic efficacy. In this study, CTCs were serially collected from patients with HCC undergoing atezolizumab plus bevacizumab (Atezo+Bev) treatment, and changes in molecular expression and CTC numbers were analyzed to identify effective biomarkers. Approach and results: The peripheral blood samples were collected serially from 22 patients with HCC treated with Atezo+Bev, and CTCs were enriched using RosetteSep. The CD45(-)PanCK(+) cell counts were measured using flow cytometry. RNA extracted from enriched CTCs underwent targeted RNA sequencing with next-generation sequencing (NGS) and performed unsupervised hierarchical clustering analysis. Changes in CTC numbers during Atezo+Bev treatment reflected the tumor volume. NGS analysis revealed that patients with elevated transforming growth factor (TGF)-β signaling molecules had a poorer response, whereas those with elevated apoptosis signaling molecules had a favorable response (p < 0.05). In addition, compared with changes in CTC counts, changes in TGF-β signaling molecule expression in CTCs accurately and promptly predicted treatment response. Conclusions: NGS analysis of CTC-derived RNA showed that changes in TGF-β signaling molecules predict treatment response earlier than changes in CTC counts. These findings suggest that changes in the expression of TGF-β molecules in CTCs could serve as novel biomarkers for the early prediction of therapeutic response in patients with unresectable HCC undergoing Atezo+Bev therapy.

2024-07-17 | GSE261186 | GEO

Bevacizumab plus chemotherapy continued beyond progression in patients with type II endometrial cancer previously treated with bevacizumab plus chemotherapy: A case report.

Project description:The prognosis of patients with recurrent/persistent endometrial cancer, particularly type II cancer, remains poor, and effective treatment has not yet been established. We herein present the case of a patient with recurrent type II endometrial cancer who received bevacizumab + chemotherapy continued beyond progression, after previously receiving bevacizumab + chemotherapy. This patient experienced recurrence after first- and second-line adjuvant chemotherapy followed by modified radical hysterectomy and she was administered bevacizumab + paclitaxel + carboplatin therapy. After six cycles of treatment, all metastatic lesions shrunk, indicating partial response. The patient next received single-agent bevacizumab as maintenance therapy. After 12 cycles of bevacizumab monotherapy, disease progression was detected; therefore, combination therapy consisting of bevacizumab, doxorubicin and carboplatin was initiated. After six cycles of this combination therapy, the patient exhibited disease stabilization. Finally, 18 months after the initial bevacizumab treatment, the patient remained on combination chemotherapy, without complaints or signs of tumor progression (last follow-up, October 2014).

| S-EPMC5530304 | biostudies-other

Assessment of tumor pathological and transcriptional biomarkers in pre- and on-treatment core biopsies predictive of response and outcome after neoadjuvant chemotherapy plus Bevacizumab in patients with HER2-negative breast cancer

Project description:Assessment of tumor pathological and transcriptional biomarkers in pre- and on-treatment core biopsies predictive of response and outcome after neoadjuvant chemotherapy plus Bevacizumab in patients with HER2-negative breast cancer: Results from a multi-center, single-arm, phase 2 study (the PROMIX trial) Global gene expression profiling was performed on samples from 3 time points (baseline, after 2 cycles and surgery) from women with breast cancer receivcing neoadjuvant chemotherapy with bevacizumab in a phase 2 trial

2017-09-01 | GSE87455 | GEO

Identification of SNP candidates associated with chemo-responsiveness in colorectal cancer patients

Project description:Response rates of 118 colorectal cancer patients to regiments were evaluated by histoculture drug response assay. Affymetrix SNP 6.0 chips were used to determine genotypes of the same colorectal cancer patients. SNPs associated with chemosensitivity to treatment regiments were identified by genome-wide association study. AV: avastin (Bevacizumab), ER: Erbitux (Cetuximab), FXA: bevacizumab + FOLFOX, FXE: Cetuximab + FOLFOX , FRA: Bevacizumab + FOLFIRI, FRE: Cetuximab + FOLFIRI; Numbers (0-100) represent responsiveness to the given drug regimens; the larger, the better responsive to given regimens

2011-03-25 | GSE21228 | GEO

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