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Lung Cancer (Amsterdam, Netherlands) May 2021Multiple immunotherapy and chemotherapy combinations are approved for the management of advanced NSCLC which have not been directly compared in randomized clinical... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Multiple immunotherapy and chemotherapy combinations are approved for the management of advanced NSCLC which have not been directly compared in randomized clinical trials. This study indirectly compared the effectiveness of pembrolizumab + chemotherapy versus atezolizumab + chemotherapy+/-bevacizumab for previously untreated non-squamous NSCLC patients without EGFR/ALK aberrations.
MATERIALS AND METHODS
A matching-adjusted indirect comparison (MAIC) was conducted using individual patient data (IPD) from KEYNOTE-021 Cohort G (KN021 G) (pembrolizumab + carboplatin + pemetrexed; N = 59) and KEYNOTE-189 (KN189) (pembrolizumab + pemetrexed + platinum chemotherapy; N = 410) and published aggregate data from IMpower 130 (atezolizumab + carboplatin + nab-paclitaxel; N = 451) and IMpower 150 (atezolizumab + carboplatin + paclitaxel + bevacizumab; N = 356). To adjust for cross-trial differences in baseline characteristics, data from patients randomized to pembrolizumab + chemotherapy in KN021 G/KN189 were reweighted to match the baseline characteristics of patients randomized to atezolizumab + chemotherapy from IMpower 130 or atezolizumab + chemotherapy + bevacizumab from IMpower 150. Outcomes included overall survival (OS), blinded independent review-assessed progression-free survival (PFS) and objective response rate (ORR). OS and PFS follow-up were truncated to the trial with shorter follow-up. Sensitivity analyses were conducted without truncation of follow-up of OS and PFS.
RESULTS
After matching for cross-trial differences, the effective sample size of pembrolizumab + chemotherapy was 428 and 389 for the IMpower 130 and IMpower 150 comparisons, respectively. The estimated HRs (95 % CIs) of pembrolizumab + chemotherapy versus atezolizumab + chemotherapy were 0.80 (0.67,0.95) and 0.79 (0.67,0.93) with regard to OS and PFS, respectively. For pembrolizumab + chemotherapy versus atezolizumab + chemotherapy + bevacizumab, the estimated HR (95 % CIs) was 0.86 (0.72,1.03) for OS and 0.81 (0.68,0.96) for PFS. For ORR, the estimated risk ratio (95 % CI) and the risk difference (95 % CI) was 0.9 (0.8,1.1) and -3.5 % (-10.0,3.1) for pembrolizumab + chemotherapy versus atezolizumab + chemotherapy, respectively, and 0.8 (0.7,0.9) and -12.2 % (-19.6,-4.8) for pembrolizumab + chemotherapy versus atezolizumab + chemotherapy + bevacizumab, respectively. Findings were consistent across sensitivity analyses for both outcomes.
CONCLUSION
MAIC results showed a significantly better OS and PFS for pembrolizumab + chemotherapy compared with atezolizumab + chemotherapy and a significantly better PFS for pembrolizumab + chemotherapy compared with atezolizumab + chemotherapy + bevacizumab.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carboplatin; Humans; Lung Neoplasms
PubMed: 33839603
DOI: 10.1016/j.lungcan.2021.03.020 -
Targeted Oncology Nov 2022A comparison between atezolizumab plus bevacizumab (ATEZO/BEVA) and lenvatinib (LEN) for the treatment of hepatocellular carcinoma (HCC) remains unclear.
Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis.
BACKGROUND
A comparison between atezolizumab plus bevacizumab (ATEZO/BEVA) and lenvatinib (LEN) for the treatment of hepatocellular carcinoma (HCC) remains unclear.
OBJECTIVE
This study aimed to compare the therapeutic effects and safety of ATEZO/BEVA and LEN as first-line therapies for HCC.
PATIENTS AND METHODS
This study was a retrospective analysis of 810 patients with HCC who underwent ATEZO/BEVA (n = 186) or LEN (n = 624) as first-line systemic therapy between March 2018 to March 2022 at 14 facilities. After propensity score matching, 304 patients (ATEZO/BEVA group: n = 152; LEN group: n = 152) were analyzed.
RESULTS
After propensity score matching, although there was no significant difference in objective response rates (ORRs) between the ATEZO/BEVA and LEN groups (ORR 44.8% vs. 46.7%, p = 0.644), the median progression-free survival (PFS) and median overall survival (OS) in the ATEZO/BEVA group were significantly higher than those in the LEN group (median PFS: 8.3 months vs. 6.0 months, p = 0.005; median OS: not reached vs. 20.2 months, p = 0.039). The rates of appetite loss, fatigue, and proteinuria of grade 3 or higher in the ATEZO/BEVA group were lower than those in the LEN group. However, the rate of bleeding of grade 3 or higher in the ATEZO/BEVA group was higher than that in the LEN group. The conversion rate was higher in the ATEZO/BEVA group than that in the LEN group (8.6% vs. 1.9%, p = 0.007).
CONCLUSIONS
ATEZO/BEVA showed superiority to LEN in terms of prognosis and conversion rate as first-line therapy. Moreover, ATEZO/BEVA had a lower rate of severe adverse events, except for bleeding, than LEN.
Topics: Humans; Carcinoma, Hepatocellular; Bevacizumab; Liver Neoplasms; Propensity Score; Retrospective Studies
PubMed: 36272060
DOI: 10.1007/s11523-022-00921-x -
United European Gastroenterology Journal Mar 2024The evolution in systemic therapies in hepatocellular carcinoma (HCC) signifies a strategy of high-cost, high-gain innovation that originated with sorafenib, despite its... (Review)
Review
The evolution in systemic therapies in hepatocellular carcinoma (HCC) signifies a strategy of high-cost, high-gain innovation that originated with sorafenib, despite its limited impact on tumor response. This strategic approach paved the way for the emergence of a second wave of the short-lived competitive advantage, exemplified by the incorporation of atezolizumab plus bevacizumab and tremelimumab plus durvalumab. In the context of safety concerns within the liver cancer domain, the IMBRAVE150 and HIMALAYA trials boldly incorporated bevacizumab and tremelimumab, respectively, demonstrating the continuation of the high-risk, high-reward innovation paradigm. This review delves into the strengths, weaknesses, opportunities, and threats analysis of systemic therapies in the field of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Bevacizumab; Liver Neoplasms; Sorafenib
PubMed: 38267015
DOI: 10.1002/ueg2.12510 -
Daru : Journal of Faculty of Pharmacy,... Apr 2015
Topics: Angiogenesis Inhibitors; Bevacizumab; Drug Compounding; Drug Stability; Humans; Intravitreal Injections
PubMed: 25896903
DOI: 10.1186/s40199-015-0110-0 -
A phase II study of bevacizumab and temsirolimus in advanced extra-pancreatic neuroendocrine tumors.Endocrine-related Cancer Nov 2023We assessed the efficacy and safety of combining bevacizumab with temsirolimus in patients with advanced extra-pancreatic neuroendocrine tumors. This NCI-sponsored...
We assessed the efficacy and safety of combining bevacizumab with temsirolimus in patients with advanced extra-pancreatic neuroendocrine tumors. This NCI-sponsored multicenter, open-label, phase II study (NCT01010126) enrolled patients with advanced, recurrent, or metastatic extra-pancreatic neuroendocrine tumors. All patients were treated with temsirolimus and bevacizumab until disease progression or unacceptable toxicity. Temsirolimus 25 mg was administered i.v. on days 1, 8, 15, and 22 and bevacizumab 10 mg/kg i.v. on days 1 and 15 of a 4-week cycle. Discontinuation of temsirolimus or bevacizumab did not require discontinuation of the other agent. The primary endpoints were objective response rate and 6-month progression-free survival rate. Fifty-nine patients were enrolled in this study, and 54 were evaluated for efficacy and adverse events. While median progression-free survival was 7.1 months, the median duration of treatment with temsirolimus was 3.9 months and that with bevacizumab was 3.5 months. The objective response rate of combination therapy was 2%, and 6-month progression-free survival was 48%. The most frequently reported grade 3-4 adverse events included fatigue (13%), hypertension (13%), and bleeding (13%). Close to 54% of the patients discontinued treatment due to adverse events, refusal of further treatment, or treatment delays. Three deaths occurred in the study, of which two were due to treatment-related bowel perforations. Given the minimal efficacy and increased toxicity seen with the combination of bevacizumab and temsirolimus, we do not recommend the use of this regimen in patients with advanced extra-pancreatic neuroendocrine tumors.
Topics: Humans; Bevacizumab; Neuroendocrine Tumors; Combined Modality Therapy; Neoplasms, Second Primary; Pancreatic Neoplasms
PubMed: 37702588
DOI: 10.1530/ERC-22-0301 -
Journal of Cancer Research and Clinical... Feb 2022Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor-specific angiogenesis in some cancers. MYL-1402O is a... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor-specific angiogenesis in some cancers. MYL-1402O is a proposed bevacizumab biosimilar.
METHODS
The primary objective of this single-center, randomized, double-blind, three-arm, parallel-group, phase 1 study in healthy male volunteers was to evaluate bioequivalence of MYL-1402O to EU and US-reference bevacizumab, and EU-reference bevacizumab to US-reference bevacizumab. The primary pharmacokinetic parameter was area under the serum concentration-time curve from 0 extrapolated to infinity (AUC). Pharmacokinetic parameters were analyzed using general linear models of analysis of variance. Secondary endpoints included safety and tolerability.
RESULTS
Of 111 enrolled subjects, 110 were included in the pharmacokinetic analysis (MYL-1402O, n = 37; EU-reference bevacizumab, n = 36; US-reference bevacizumab, n = 37). Bioequivalence was demonstrated between MYL-1402O and EU-reference bevacizumab, MYL-1402O and US-reference bevacizumab, and between EU- and US-reference bevacizumab where least squares mean ratios of AUC were close to 1, and 90% CIs were within the equivalence range (0.80-1.25). Secondary pharmacokinetic parameters (AUC from 0 to time of last quantifiable concentration [AUC], peak serum concentration [C], time to C, elimination rate constant, and elimination half-life) were also comparable, with 90% CIs for ratios of AUC and C within 80-125%. Treatment-emergent adverse events were similar across all three treatment groups and were consistent with clinical data for bevacizumab.
CONCLUSION
MYL-1402O was well tolerated and demonstrated pharmacokinetic and safety profiles similar to EU-reference bevacizumab and US-reference bevacizumab in healthy male volunteers. No new significant safety issues emerged (ClinicalTrials.gov, NCT02469987; ClinicalTrialsRegister.eu EudraCT, 2014-005621-12; June 12, 2015).
Topics: Adolescent; Adult; Bevacizumab; Biosimilar Pharmaceuticals; Double-Blind Method; Drug Compounding; Europe; Healthy Volunteers; Humans; Male; Middle Aged; Netherlands; Therapeutic Equivalency; United States; Young Adult
PubMed: 33866430
DOI: 10.1007/s00432-021-03628-0 -
CNS Oncology 2015Glioblastoma (GBM) is the most common adult primary brain neoplasm. Despite advances in treatment, GBM continues to be associated with considerable morbidity and... (Review)
Review
Glioblastoma (GBM) is the most common adult primary brain neoplasm. Despite advances in treatment, GBM continues to be associated with considerable morbidity and mortality as compared with other malignancies. Standard treatment for GBM results in survival of 12.9 months (95% CI: 12.3-13.7 months) with a median progression-free survival of 7.2 months (95% CI: 6.4-8.2 months) in a modern GBM cohort. These aggressive tumors recur and treatment for recurrent GBM continues to have very poor outcomes. Prior to the use of bevacizumab, monoclonal antibody to VEGF, 6-month progression-free survival in clinical trials for recurrent GBM ranged from 9 to 15%. Trials utilizing bevacizumab and its subsequent US FDA approval have given more hope to recurrent GBM and this concise review discusses bevacizumab in recurrent GBM. This review focuses on time-to-event outcomes (overall survival, progression-free survival and 6-month progression-free survival) in clinical trials utilizing bevacizumab for the treatment of recurrent GBM. For this review, we have chosen to focus primarily on Phase II clinical trials that have been published and available in the literature (PubMed). While we focused primarily on time-to-event variables, toxicity and safety of bevacizumab is very important and this agent can be associated with serious life-threatening toxicities. We have included a general section of toxicities but for a more lengthy review please see the excellent study by Odia and colleagues.
Topics: Angiogenesis Inhibitors; Bevacizumab; Brain Neoplasms; Clinical Trials as Topic; Female; Glioblastoma; Humans; Male
PubMed: 25906439
DOI: 10.2217/cns.15.8 -
In Vivo (Athens, Greece) 2019The aim of this study was to evaluate the efficacy of bevacizumab combined with cisplatin and paclitaxel for persistent, recurrent, or metastatic cervical cancer.
BACKGROUND/AIM
The aim of this study was to evaluate the efficacy of bevacizumab combined with cisplatin and paclitaxel for persistent, recurrent, or metastatic cervical cancer.
MATERIALS AND METHODS
This is a retrospective review of medical records of patients with persistent, recurrent, or metastatic cervical cancer.
RESULTS
Of the 52 patients, 33 (63.5%), 7 (13.5%) and 12 (23.1%) had recurrent, persistent and metastatic disease, respectively. Twenty-seven patients (51.9%) had prior platinum exposure. Possible bevacizumab-related serious adverse events included hypertension (n=3/52, 5.8%), febrile neutropenia (n=4/52, 7.7%) and fistula (n=2/52, 3.8%). Thirty-two recurrences (61.5%) and 20 deaths (38.5%) were noted. Median progression-free and overall survival was 9.8 months and 15.3 months, respectively. Recurrence included loco-regional (17/32, 59.4%), nodal (11/32, 34.4%), distant site (10/32, 31.3%) and peritoneal seeding (6/32, 18.8%).
CONCLUSION
Bevacizumab with cisplatin and paclitaxel for treating persistent, recurrent or metastatic cervical cancer is feasible and well tolerated. Loco-regional recurrence was most frequent. Overall survival was worse with recurrence at >2 sites or distant metastases.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Combined Modality Therapy; Female; Humans; Kaplan-Meier Estimate; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Recurrence; Retreatment; Retrospective Studies; Treatment Outcome; Uterine Cervical Neoplasms
PubMed: 31028209
DOI: 10.21873/invivo.11551 -
Drugs in R&D Sep 2023BAT1706 is a proposed biosimilar of bevacizumab, a vascular endothelial growth factor A (VEGF-A)-targeting biologic used to treat several different cancers, including...
BACKGROUND
BAT1706 is a proposed biosimilar of bevacizumab, a vascular endothelial growth factor A (VEGF-A)-targeting biologic used to treat several different cancers, including metastatic colorectal cancer. A comprehensive physicochemical and functional similarity assessment is a key component of demonstrating biosimilarity between a reference biologic and a proposed biosimilar. Here we report the physicochemical and functional similarity of BAT1706 and reference bevacizumab sourced from both the United States (US-bevacizumab) and the European Union (EU-bevacizumab).
METHOD
A large range of product attributes, including primary and higher order structure, post-translational modifications, purity, stability, and potency, were characterized for BAT1706 and EU/US-bevacizumab using sensitive state-of-the-art analytical techniques. Up to 18 lots of US- and 29 lots of EU-bevacizumab, and 10 unique drug substance lots of BAT1706, were assessed.
RESULT
BAT1706 was shown to have an identical amino acid sequence and an indistinguishable higher-order structure compared with EU/US-bevacizumab. BAT1706 and EU/US-bevacizumab also exhibited similar post-translational modifications, glycan profiles, and charge variants. Potency, assessed using a wide range of bioassays, was also shown to be comparable between BAT1706 and EU/US-bevacizumab, with statistical equivalence demonstrated for VEGF-A binding and neutralizing activity.
CONCLUSION
Overall, this extensive comparability exercise demonstrated BAT1706 to match EU/US-bevacizumab in terms of all physicochemical and functional attributes assessed.
Topics: Humans; Bevacizumab; Vascular Endothelial Growth Factor A; Biosimilar Pharmaceuticals; Biological Assay; Phosphorylation
PubMed: 37479945
DOI: 10.1007/s40268-023-00432-8 -
Journal of Translational Medicine Feb 2023Neovascular age-related macular degeneration (nAMD) is a major cause of visual impairment and blindness. Anti-vascular endothelial growth factor (VEGF) agents, such as... (Review)
Review
Neovascular age-related macular degeneration (nAMD) is a major cause of visual impairment and blindness. Anti-vascular endothelial growth factor (VEGF) agents, such as ranibizumab, bevacizumab, aflibercept, brolucizumab and faricimab have revolutionized the clinical management of nAMD. However, there remains an unmet clinical need for new and improved therapies for nAMD, since many patients do not respond optimally, may lose response over time or exhibit sub-optimal durability, impacting on real world effectiveness. Evidence is emerging that targeting VEGF-A alone, as most agents have done until recently, may be insufficient and agents that target multiple pathways (e.g., aflibercept, faricimab and others in development) may be more efficacious. This article reviews issues and limitations that have arisen from the use of existing anti-VEGF agents, and argues that the future may lie in multi-targeted therapies including alternative agents and modalities that target both the VEGF ligand/receptor system as well as other pathways.
Topics: Humans; Angiogenesis Inhibitors; Macular Degeneration; Ranibizumab; Bevacizumab; Recombinant Fusion Proteins; Intravitreal Injections
PubMed: 36810060
DOI: 10.1186/s12967-023-03937-7