SynthesisJournal of the National Cancer Institute2020
A Systematic Review and Meta-Analysis of Bevacizumab in First-Line Metastatic Breast Cancer: Lessons for Research and Regulatory Enterprises.
Synthesis in Journal of the National Cancer Institute, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 citations in OpenAlex.
- Efficacy and Safety of Bevacizumab in Pretreated Metastatic Breast Cancer: A Systematic Review and Meta-Analysis.Oncology research and treatment · 2022Pooled it
- 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5).Annals of oncology : official journal of the European Society for Medical Oncology · 2020Guideline
- Efficacy and safety of camrelizumab combined with apatinib in advanced triple-negative breast cancer: an open-label phase II trial.Journal for immunotherapy of cancer · 2020Trial
- E7389-LF as a first-line chemotherapy for patients with metastatic/advanced HER2-negative breast cancer: results from the phase 1 dose-expansion part of study 114.Breast cancer research : BCR · 2026Article
- EID1 blockade potentiates immunosurveillance against cancer metastasis via FPR1-mediated DC-NK crosstalk.Science China. Life sciences · 2026Article
- Endothelial activation during the diapedesis of cancer cells: between the kiss of death and therapeutic breakthrough.Cellular & molecular biology letters · 2025Review
- Triple-Negative Breast Cancer Unveiled: Bridging Science, Treatment Strategy, and Economic Aspects.International journal of molecular sciences · 2025Review
- Revealing the Angiogenic Signature ofCancers · 2025Article
- Pan-cancer human brain metastases atlas at single-cell resolution.Cancer cell · 2025Article
- Invasion and metastasis in cancer: molecular insights and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Disease-free survival as a surrogate for overall survival in early-stage pancreatic cancer trials: a correlation meta-analysis.BMJ oncology · 2025Article
- Frequently asked questions on surrogate endpoints in oncology-opportunities, pitfalls, and the way forward.EClinicalMedicine · 2024Review
- SEOM-GEICAM-SOLTI clinical guidelines in advanced breast cancer (2022).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Risk Factors for Bisphosphonate-Related Osteonecrosis of the Jaws in Bone Metastatic Breast and Prostate Cancer under Zoledronate Treatment: A Retrospective Analysis from 10 Years of Evaluation.Asian Pacific journal of cancer prevention : APJCP · 2023Observational
- Expedited regulatory product approval in the time of COVID-19.The ocular surface · 2022Article
- Front-Line Bevacizumab plus Chemotherapy with or without Maintenance Therapy for Metastatic Breast Cancer: An Observational Study by the Hellenic Oncology Research Group.Current oncology (Toronto, Ont.) · 2022Observational
- Inflammatory cytokines and distant recurrence in HER2-negative early breast cancer.NPJ breast cancer · 2022Article
- Monoclonal antibodies and chimeric antigen receptor (CAR) T cells in the treatment of colorectal cancer.Cancer cell international · 2021Review
- A correlation analysis to assess event-free survival as a trial-level surrogate for overall survival in early breast cancer.EClinicalMedicine · 2021Article
- Bevacizumab Plays a double-edged role in Neoadjuvant Therapy for Non-metastatic Breast Cancer: A Systemic Review and Meta-Analysis.Journal of Cancer · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe US Food and Drug Administration's accelerated approval and later withdrawal of bevacizumab in patients with metastatic breast cancer (mBC) is a seminal case for ongoing debates about the validity of using progression-free survival (PFS) as a surrogate measure for overall survival (OS) in cancer drug approvals. We systematically reviewed and meta-analyzed the evidence around bevacizumab's regulatory approval and withdrawal in mBC.
methodsWe searched for all published phase II or III clinical trials testing bevacizumab as a first-line therapy for patients with mBC. Data were extracted on trial demographics, interventions, and outcomes. Descriptive analysis was stratified by whether the trial was initiated before, during, or after the accelerated approval. We used a cumulative random-effects meta-analysis to assess the evolution of evidence of the effect of bevacizumab on PFS and OS. We estimated the association between the trial-level PFS and OS effect using a nonlinear mixed-regression model.
resultsFifty-two studies were included. Trial activity dramatically dropped after the accelerated approval was withdrawn. Eight clinical trials reported hazard ratios (hazard ratios) and were meta-analyzed. The cumulative hazard ratio for PFS was 0.72 (95% CI = 0.65 to 0.79), and the cumulative hazard ratio for OS was 0.90 (95% CI = 0.80 to 1.01). The regression model showed a statistically nonsignificant association between PFS benefit and OS benefit (β = 0.43, SE = 0.81).
conclusionThe US Food and Drug Administration's decision-making in this case was consistent with the evolving state of evidence. However, the fact that seven clinical trials are insufficient to conclude validity (or lack thereof) for a trial-level surrogate suggests that it would be more efficient to conduct trials using the more clinically meaningful endpoints.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.