Avastin (bevacizumab)

Bevacizumab demonstrates effectiveness in managing VS, particularly in NF2 patients, by reducing tumor size and preserving hearing in a substantial proportion of cases. However, the variability in patient response and the risk of adverse events underscore the need for individualized treatment approaches and further research, including randomized controlled trials, to optimize its clinical application.

In IDH-wildtype glioblastoma patients, a history of other precedent cancer was associated with worse overall survival (OS), while re-operation and bevacizumab therapy increased OS...Nine patients received molecular targeted therapy, and the results were evaluated. The search for molecular changes associated with tumor growth and progression is important for diagnosis and choice of therapy.

Our data show that baseline serum levels of hepcidin are an independent risk factor for OS in MSS mCRC patients undergoing standard first-line treatment. Further prospective and extensive studies are needed to confirm and validate our findings.

The management of metastatic colorectal cancer in patients harboring RAS mutations primarily involves chemotherapy, often combined with bevacizumab, as a standard first-line treatment...Further research is needed to validate these mechanisms and understand the impact of the neo-RAS wt phenomenon on long-term outcomes, such as overall survival and progression-free survival. This review provides a comprehensive overview of the current understanding of the neo-RAS wt phenomenon, including its incidence, potential mechanisms, and clinical implications.

P1/2, N=48, Recruiting, University Health Network, Toronto | Not yet recruiting --> Recruiting

P2, N=90, Recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Not yet recruiting --> Recruiting

P2, N=105, Recruiting, Qilu Hospital of Shandong University

P3, N=100, Completed, Roche Farma S.A.

P1/2, N=518, Recruiting, Hoffmann-La Roche | Trial completion date: Aug 2026 --> Dec 2026 | Trial primary completion date: Aug 2026 --> Dec 2026

P2, N=73, Not yet recruiting, UNICANCER | Initiation date: Oct 2024 --> Jan 2025

P3, N=238, Recruiting, Gruppo Oncologico del Nord-Ovest

P3, N=49, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting | N=100 --> 49

P1/2, N=360, Not yet recruiting, Bristol-Myers Squibb

P1/2, N=6, Terminated, ImmunityBio, Inc. | N=80 --> 6 | Unknown status --> Terminated; Study halted prematurely and will not resume; participants are no longer being examined or receiving intervention

P3, N=1147, Recruiting, Bristol-Myers Squibb | N=831 --> 1147 | Trial primary completion date: Jun 2025 --> Aug 2024

Through modulating these tumour biological characteristics via ALDH1, bevacizumab increases the sensitivity of cervical carcinoma to cisplatin, suggesting that bevacizumab in combination with standard chemotherapy may represent a new strategy for overcoming drug resistance. Abbreviation: HPV, human papillomavirus; CSCs, cancer stem cells; ALDH1, aldehyde dehydrogenase 1; EMT, epithelial-mesenchymal transition; OD, optical density; qRT-PCR, RNA analysis by quantitative real-time polymerase chain reaction; RIPA, radioimmunoprecipitation assay; SDS-PAGE, sodium dodecyl sulphate-polyacrylamide gel electrophoresis; PVDF, polyvinylidene difluoride; ECL, electrochemiluminescence; NC, negative control; HE, haematoxylin and eosin; IHC, immunohistochemistry; DAB, 3, 3'-diaminobenzidine; IF, immunofluorescence; DAPI, 4,6-diamidino-2-phenylindole; VEGFA, vascular endothelial growth factor A; ROS, oxygen species; DFS, disease-free survival; OS, overall survival; HIF, hypoxia-inducible factor; PDGFs, platelet-derived growth factors; FGFs, fibroblast growth factors; PlGF, placenta growth factor; RTKs, receptor tyrosine kinases.

P2, N=70, Recruiting, Li-kun Chen

This phase 2 trial (NCT04324476) aimed to evaluate efficacy and safety of alternating modified CAPOX (capecitabine and oxaliplatin)/modified CAPIRI (capecitabine and irinotecan) plus bevacizumab (anti-VEGF-A antibody) in untreated unresectable mCRC...Thus, alternating modified CAPOX/CAPIRI plus bevacizumab had promising efficacy and acceptable safety. The regimen may be a novel option for untreated unresectable mCRC.

P2, N=27, Recruiting, Northwestern University | Trial completion date: Aug 2024 --> Dec 2026 | Trial primary completion date: Sep 2023 --> Sep 2026

P1/2, N=48, Not yet recruiting, University Health Network, Toronto

Targeted therapy, the milestone in the development of human medicine, originated in 2004 when the FDA approved the first targeted agent bevacizumab for colorectal cancer treatment...However, the efficacy of targeted therapy is extremely variable, especially with the emergence of new drugs and the innovative use of traditional targets for other tumors in recent years. Accordingly, this review provides an overview of the major signaling pathway mechanisms and recent advances in targeted therapy for gastrointestinal cancers, as well as future perspectives.

Serum IL-6 levels are thought to be involved in the suppression of tumor immunity and are useful in predicting the therapeutic effect of Atezo+Bev treatment.

P2, N=120, Active, not recruiting, University of California, Irvine | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P1, N=498, Recruiting, Genentech, Inc. | Trial completion date: Nov 2024 --> Mar 2026 | Trial primary completion date: Nov 2024 --> Mar 2025

P2, N=24, Active, not recruiting, Yale University | Recruiting --> Active, not recruiting

For the in vitro study, an MTT assay was performed, and then different combinations against the THP-1 cell line were used as follows: non-treated cells, THP-1/ATOR IC50, THP-1/cytarabine (CYT) IC50, THP-1/doxorubicin (DOX) IC50, THP-1/DOX/CYT, THP-1/ATOR/CYT, THP-1/ATOR/DOX, and THP-1/ATOR/CYT/DOX...G4 was treated with Bevacizumab (Bev) (5 mg/kg)...Furthermore, in vivo co-treatment with ATOR/Bev decreased tumor incidence and size with a significant reduction of the immunohistochemical PCNA (LI%) in lung parenchyma, targeting PI3K/Akt/mTOR, and VEGF-A signaling pathways. Co-treatment with ATOR and chemotherapies led to cell cycle arrest, modulation of the PI3K/Akt/mTOR, and VEGF-A signaling pathways in tumor cells.

With >5 years of follow-up, responses to pembrolizumab remained durable. Median OS was over twice as long in patients treated with pembrolizumab versus chemotherapy in first line despite an effective crossover rate of 62%. Pembrolizumab remains a standard of care for MSI-H/dMMR mCRC.

Multi-omics and treatment response data from 115 samples of 49 patients with CRLM undergoing bevacizumab (BVZ)-based chemotherapy show little difference in genomic alterations in 92% of cases, while remarkable differences are observed at the transcriptomic level...Gene interference experiments suggest that SMAD4R361H/C mutations confer BVZ and 5-fluorouracil (5-FU) resistance through STAT3 signaling. Notably, supplementing BVZ and 5-FU with the STAT3 inhibitor GB201 restores therapeutic efficacy in SMAD4R361H/C cancer cells. Our study uncovers the evolutionary dynamics of CRLM and its microenvironment during treatment and offers strategies to overcome drug resistance.

P1, N=518, Completed, Genentech, Inc. | Active, not recruiting --> Completed

P2, N=14, Active, not recruiting, Case Comprehensive Cancer Center | Trial completion date: Oct 2024 --> Apr 2025 | Trial primary completion date: Oct 2024 --> Apr 2025

P1, N=49, Active, not recruiting, Wuhan Union Hospital, China

P2, N=32, Not yet recruiting, University of Saskatchewan | Trial completion date: Mar 2026 --> Dec 2026 | Trial primary completion date: Mar 2026 --> Dec 2026

The randomized FIRE-4.5 (AIO KRK0116) trial compared first-line therapy with FOLFOXIRI (folinic acid, fluorouracil, oxaliplatin, and irinotecan) plus either cetuximab or bevacizumab in B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E-mutant metastatic colorectal cancer (mCRC) patients. Those patients also achieved a significantly greater disease control rate (89% vs 20%; P = 0.008). In conclusion, LB evaluating ctDNA is informative and may help to guide treatment in patients with BRAF V600E-mutated mCRC.

Five months after, the patient complained of abdominal pain, with an alpha-fetoprotein (AFP) level exceeding 9000 ng/ml, and CT images showed liver metastases and multiple lung metastases, so treatment with immunotherapy atezolizumab plus bevacizumab was started in September 2022. However, abdominal pain improved, and AFP decrease, raising suspicion of pseudoprogression. Treatment was therefore continued until radiological progression could be confirmed with a follow-up CT scan after 2 months, which revealed a complete response of the pulmonary metastasis and a partial response of the liver metastasis.

P1, N=5, Active, not recruiting, City of Hope Medical Center | Trial completion date: Nov 2024 --> Jun 2025 | Trial primary completion date: Nov 2024 --> Jun 2025

P2, N=73, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

P1, N=11, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jan 2025 --> Jun 2025

P3, N=430, Recruiting, Chipscreen Biosciences, Ltd. | Not yet recruiting --> Recruiting

P1/2, N=36, Active, not recruiting, Sun Yat-sen University | Trial completion date: Oct 2024 --> Oct 2025

The side effects were mild to moderate hand-foot-syndrome, hypertension, and proteinuria. Afatinib in combination with bevacizumab are effective and safe in the management of patients with NSCLC harboring EGFR G719X, S768I, L861Q/P single or compound mutations.

MIRV as ≥3L treatment in heavily pretreated recurrent FRα-positive PSOC demonstrated notable efficacy and tolerable safety, including among those with prior PD on or within 30 days of PARPi. (Funding, ImmunoGen, Inc; NCT05041257).

P2, N=153, Completed, Hospices Civils de Lyon | Active, not recruiting --> Completed