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REVIEW 4 major objections 5 minor 81 references

Visualisation of multi-indication randomised control trial evidence to support decision-making in oncology: a case study on bevacizumab

T0 review · 4 major / 5 minor · reviewed 2026-08-10 · deepseek-v4-flash

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Pith's one-line read Clear graphical maps of a drug's evidence across all its licensed cancer types can reveal when trial results are exchangeable and support decisions about borrowing evidence across indications.

desk verdict Useful visualisation framework for multi-indication oncology evidence, but the bevacizumab case study rests on a supplementary table with apparent transcription errors that need correcting before the quantitative claims can be trusted. read the letter →

arxiv 2501.08744 v1 pith:XO4AMBML submitted 2025-01-15 stat.AP

Sumayya Anwer , Janharpreet Singh , Sylwia Bujkiewicz , Anne Thomas , Richard Adams , Elizabeth Smyth , Pedro Saramago , Stephen Palmer
show 2 more authors
Marta O Soares Sofia Dias
This is my paper · ORCID
classification stat.AP
keywords evidencevisualisationmulti-indicationdrugsbevacizumabhealthtechnologyassessmentcumulativemeta-analysisridgelineplotssynthesisoncology
verification ladder T0 review T1 audit T2 compute T3 formal

The pith

A machine-rendered reading of the paper's core claim, the machinery that carries it, and where it could break.

The reading

This paper argues that a drug licensed for several cancer types should not be appraised using only the evidence from one indication. It develops three kinds of plots, timelines, ridgeline plots, and split-violin plots, that lay out the full bevacizumab evidence base across seven licensed cancer types, showing when trials ran, when results were reported, how mature and precise the estimates are, and how pooled estimates change under different evidence-sharing assumptions. The maps are meant to give health technology assessment analysts a visual basis for judging whether the drug's effect is similar enough across indications to borrow information across them. The case study suggests that the log hazard-ratio densities for overall and progression-free survival overlap within and across indications, so borrowing across indications is plausible for bevacizumab.

What carries the argument

The carrying objects are three plot types and three synthesis models. Timeline plots put every trial on a shared time axis so that the accumulation, size, precision, and maturity of evidence can be seen as it appears; ridgeline plots stack the distribution of each reported log hazard ratio by year so that the overlap of densities across indications can be judged directly; split-violin plots place two distributions on either side of a central line to compare overall and progression-free survival across models. The quantitative machinery is the cumulative meta-analysis under three sharing assumptions: the independent-parameter model (no borrowing), the common-parameter model (complete borrowing), and the hierarchical meta-analysis model (borrowing moderated by between-indication heterogeneity), all run in a Bayesian random-effects framework. The plots work by substituting entire densities for point estimates, so the visible overlap of curves becomes the evidence for exchangeability.

What would settle it

Re-run the data assembly with a comprehensive systematic search, redraw the ridgeline plots, and formally estimate between-indication heterogeneity; if the log hazard-ratio densities separate by indication or if the between-indication standard deviation in the hierarchical model is large, the paper's visual case for exchangeability fails.

Watch

Extended reading notes

Core claim

Using 41 randomised controlled trials across seven licensed indications of bevacizumab, the paper constructs evidence maps that display the evolution of overall survival and progression-free survival estimates over more than two decades. The central visual claim is that ridgeline plots, which draw the full density of each trial's reported log hazard ratio instead of only a point estimate and confidence interval, show the curves overlapping within and across indications; the authors read this as suggesting that the treatment effect of bevacizumab is similar across indications. They then fit three cumulative meta-analysis models, no borrowing, complete borrowing, and hierarchical partial borrowing, and show with split-violin plots that the model results are largely consistent, with the no-borrowing model being the least precise. The paper's conclusion is that such graphical summaries give a better understanding of the whole evidence base and can inform judgements about which cross-indication assumptions to make in evidence synthesis for health technology assessment.

Load-bearing premise

The visual case for cross-indication similarity rests on the 41 trials found by searches the authors themselves call non-comprehensive, so the overlapping densities could change if missing trials reported different effects.

Editorial extensions

If this is right

  • Health technology assessment analysts can use timeline maps to see at a glance how many trials, how much follow-up, and how precise the results are for each indication before deciding whether to borrow evidence.
  • The overlapping ridgeline curves give a visual, model-free argument that bevacizumab's effect is exchangeable across indications, making cross-indication borrowing more defensible.
  • Cumulative meta-analysis displays show that after roughly three studies per indication the pooled estimate stabilises, so later results mostly add precision rather than changing the effect.
  • Because the common-parameter model gives the most precise estimates but rests on the strongest assumption, the split-violin comparisons make the precision-bias trade-off explicit and place it before the analyst for discussion.
  • The displays are updateable: as trials report interim or final outcomes, new points and new pooled densities can be added without changing the plotting machinery.

Reading between the lines

Editorial extensions of the paper, not claims the author makes directly.

  • The same display grammar could be applied to other multi-indication drugs, and the visual overlap of densities would provide a quick screening test for whether cross-indication borrowing is worth modelling.
  • A natural extension would be to add a quantitative rule of thumb to the split-violin plots, such as the posterior probability that indication-specific effects differ, so that the visual judgement can be audited.
  • Because progression-free survival is reported earlier and often more precisely than overall survival, the displays could support borrowing on progression-free survival while overall survival evidence is still immature, with the overall survival timeline as a running check on that choice.
  • The ridgeline overlap is read from an incomplete evidence base, so the plots should be treated as a decision-support display rather than a formal exchangeability test.
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Editorial analysis

A structured set of objections, weighed in public.

Desk editor's note, referee report, and a circularity audit.

Referee Report

4 major / 5 minor

Summary. The paper develops and demonstrates visualisation tools—timeline, ridgeline, and split-violin plots—for comparing randomised controlled trial evidence across multiple indications of a single oncology drug, using bevacizumab as a case study. The authors assemble a dataset of 41 trials across seven licensed cancer types, extract hazard ratios for overall and progression-free survival, fit three Bayesian hierarchical meta-analysis models (independent, common, and hierarchical), and display cumulative meta-analysis results over time. The central claim is that such graphical representations help analysts judge whether treatment effects are similar across indications and whether cross-indication borrowing is appropriate; the authors assert that the ridgeline plots show overlapping curves within and across indications, suggesting similar bevacizumab effects.

Significance. If the underlying data and analyses are correct, the paper offers a genuinely useful and practical visualisation toolkit for health technology assessment, where multi-indication drugs are increasingly common. The use of standard Bayesian meta-analysis models with weakly informative priors is methodologically defensible, and the case-study demonstrates how these displays can support decisions about evidence borrowing. The value of the contribution depends on the integrity of the extracted data and the reproducibility of the figures. The paper does not provide code or a machine-readable dataset, and the supplementary tables contain several apparent transcription errors that propagate into the cumulative meta-analyses and the cross-indication overlap claim. These issues are fixable but are currently load-bearing for the case-study demonstration.

major comments (4)
  1. [Supplementary Table S2 (data extraction, OS)] Table S2 contains multiple apparent transcription errors in extracted hazard ratios. E3200 OS is reported as 0.75 (0.63, 1.89), whereas the published Giantonio (2007) result is 0.75 (0.63, 0.89). RIBBON-2 OS is listed as 0.90 (0.71, 1.33), while the published Brufsky (2011) value is 0.90 (0.71, 1.14). AVF2107 OS appears as '066 (0.52, 0.84)', missing the leading zero and decimal point. These errors directly change the standard errors used in the cumulative meta-analyses, and because E3200 enters the colorectal cumulative OS analysis early, its inflated CI materially underweights a key trial. The pooled estimates in Tables S4/S5 and the density curves in Figures 4-6 are built from these entries, so the cross-indication overlap conclusion in Section 5.2 is not robust to the current data. The authors must correct the table, re-run the analyses, and verify that the displayed patterns and conclusions remain unchanged.
  2. [Section 5.3 and Supplementary Tables S4/S5] The cumulative meta-analysis results and the split-violin comparisons depend entirely on the extracted HRs and their CIs. Because no code or machine-readable dataset is provided, the effect of the transcription errors above cannot be independently assessed. Given that at least three OS entries in Table S2 are demonstrably wrong, the authors should either supply the cleaned dataset and analysis code or report a full re-analysis of all results, including Tables S4-S7 and Figures 4-6, after correcting the extracted data.
  3. [Section 6 (Discussion, limitations)] The authors acknowledge that 'due to time and resource constraints the searches conducted were not comprehensive.' This limitation is appropriate, but it applies to the central claim that the observed overlap of treatment effects across indications supports similarity. If important trials were missed, the ridgeline plot overlap and the cumulative meta-analysis comparisons could change. The manuscript should explicitly temper the conclusion that bevacizumab's effect is similar across indications, presenting it as conditional on the assembled, non-exhaustive evidence base rather than as a general finding.
  4. [Section 3.3.1 and Figures 3(d), S2, S3] The maturity visualisations are severely limited by the very low number of trials reporting event counts—as the authors note in Section 5.1 and 6, most entries in Tables S2 and S3 are 'NR' for events. This means the maturity plots convey little comparative information across indications. Since the paper presents maturity as one of the key features to display, the authors should either present a quantitative summary of how many trials contributed usable maturity data or explicitly downgrade the maturity visualisation from a demonstrated tool to a prototype that requires more complete reporting.
minor comments (5)
  1. [Supplementary Table S2 (AVF2107)] The entry '066 (0.52, 0.84)' should read '0.66 (0.52, 0.84)'; the missing leading zero and decimal point is a typographical error that would confuse any reader attempting to reproduce the data.
  2. [Supplementary Table S3 (E3200 PFS)] The PFS entry for E3200 is given as '0.61 (0.48, 078)', which is missing a decimal point before 78; it should be '0.61 (0.48, 0.78)'.
  3. [Table S5 (Glioblastoma, 31/12/2012)] The within-indication SD entry '0.231 (0.015, 0.910 0.166' is missing a closing parenthesis and appears to concatenate two numbers; this should be corrected.
  4. [Figure 2 and Section 5.1] The text states that an arbitrary gap of 2 months was added between reporting points to avoid overlap; this should be clearly noted in the figure caption, not only in the body text, so that readers do not interpret the timeline positions as exact dates.
  5. [Section 5.2, Figure 4] The ridgeline plots for colorectal, breast, and ovarian cancers are described as 'difficult to interpret' due to clustering; the supplementary ordered plots (Figure S6) help, but the main-text figures could benefit from an explicit visual cue (e.g., colour or faceting) to make the overlap claim easier to verify.

Circularity Check

0 steps flagged · score 1.0 of 10

No significant circularity; external trial data and fully specified Bayesian models drive the visualisations, with only a minor non-load-bearing self-citation.

full rationale

The paper builds its displays from externally reported trial hazard ratios and runs standard Bayesian hierarchical meta-analysis models (independent parameter, common parameter, and hierarchical meta-analysis) that are fully specified in Supplementary Section B with weakly informative priors. The cross-indication similarity claim in Section 5.2 is a descriptive reading of the plotted densities of extracted log-hazard ratios, not a model prediction used to justify those same data; the claim is independently checkable against the cited trial publications. The cumulative meta-analyses are repeated model fits rather than predictions, so no fitted parameter is relabelled as an outcome. The only self-referential element is the repeated citation of Singh et al. (reference 30) for implementation code and for discussion of more complex models; the modelling assumptions themselves are given in the supplement and are not imported as an unverified black box. The acknowledged limitation of non-comprehensive searches (Section 6) and the possible transcription errors in Table S2 flagged by the skeptic would affect data accuracy, not the circularity of the reasoning. Score 1 reflects a minor, non-load-bearing self-citation; the central derivation remains self-contained against external evidence.

Assumptions & free parameters 0 free parameters · 6 assumptions · 0 invented entities

No free parameters are fitted ad hoc; the Bayesian models estimate treatment effects and heterogeneity from the trial data, with priors taken from published methodology. The key load-bearing assumptions are the exchangeability assumptions for the borrowing models, the grouping of different chemotherapy comparators, and the completeness of the assembled trial list, which the authors themselves flag as limited.

assumptions (6)
  • standard math Random-effects normal-normal hierarchical model for ln(HR) with known within-study variances (Equations 1-2).
    Section B-I: standard meta-analysis assumption; within-study SEs are taken from reported 95% CIs.
  • standard math Weakly informative half-normal priors on heterogeneity scales, N(0,0.5^2), and vague N(0,1000) priors on pooled effects.
    Section B-I, Equations (3)-(4); priors from Rover et al. 2021, cited as reference 66.
  • domain assumption Exchangeability of bevacizumab treatment effects across indications under the CP and HMA models.
    Section 4.1: the HMA model assumes indication-level parameters are fully exchangeable around a common mean, and the observed ridgeline overlap is taken as visual support.
  • domain assumption Trials with different chemotherapy backbones can be grouped because bevacizumab's effect is unlikely to differ across chemotherapies.
    Section 5.1: following clinical advice, the authors did not differentiate between chemotherapy regimens in the comparator grouping.
  • domain assumption Only licensed indications in the advanced or metastatic setting are relevant; adjuvant, neo-adjuvant, and non-licensed indications are excluded.
    Section 2.1 exclusion criteria; the authors argue treatment effects in non-licensed indications may differ from licensed ones.
  • domain assumption Where only month and year of data cut-off were reported, the first day of that month was assumed.
    Footnotes to Tables S2 and S3; this affects timeline positions but not the extracted hazard ratios.

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Cite this review

Pith. "Pith review of Visualisation of multi-indication randomised control trial evidence to support decision-making in oncology: a case study on bevacizumab." pith.science (2026). https://pith.science/paper/XO4AMBML

@misc{pith2026250108744,
  author       = {Pith},
  title        = {Pith review of: Visualisation of multi-indication randomised control trial evidence to support decision-making in oncology: a case study on bevacizumab},
  year         = {2026},
  howpublished = {\url{https://pith.science/paper/XO4AMBML}},
  note         = {Machine review of arXiv:2501.08744}
}
read the original abstract

Background: Evidence maps have been used in healthcare to understand existing evidence and to support decision-making. In oncology they have been used to summarise evidence within a disease area but have not been used to compare evidence across different diseases. As an increasing number of oncology drugs are licensed for multiple indications, visualising the accumulation of evidence across all indications can help inform policy-makers, support evidence synthesis approaches, or to guide expert elicitation on appropriate cross-indication assumptions. Methods: The multi-indication oncology therapy bevacizumab was selected as a case-study. We used visualisation methods including timeline, ridgeline and split-violin plots to display evidence across seven licensed cancer types, focusing on the evolution of evidence on overall and progression-free survival over time as well as the quality of the evidence available. Results: Evidence maps for bevacizumab allow for visualisation of patterns in study-level evidence, which can be updated as evidence accumulates over time. The developed tools display the observed data and synthesised evidence across- and within-indications. Limitations: The effectiveness of the plots produced are limited by the lack of complete and consistent reporting of evidence in trial reports. Trade-offs were necessary when deciding the level of detail that could be shown while keeping the plots coherent. Conclusions: Clear graphical representations of the evolution and accumulation of evidence can provide a better understanding of the entire evidence base which can inform judgements regarding the appropriate use of data within and across indications. Implications: Improved visualisations of evidence can help the development of multi-indication evidence synthesis. The proposed evidence displays can lead to the efficient use of information for health technology assessment.

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Reference graph

Works this paper leans on

81 extracted references · 77 canonical work pages

  1. [1]

    Independent parameter (IP) model As there is no evidence sharing across indications, a vague normal prior distribution, ~ (0,1000)jdN is used for the pooled, indication-specific relative treatment effect, jd for each indication

    work page

  2. [2]

    This common/pooled RTE is assigned a vague normal prior distribution, ~ (0,1000)dN

    Common parameter (CP) model In this model there is complete sharing of information, jd is replaced by a common parameter, d in equation (2), which pools treatment effects across all indications. This common/pooled RTE is assigned a vague normal prior distribution, ~ (0,1000)dN

    work page

  3. [3]

    The pooled parameter dm is assigned a vague normal prior distribution and a weakly informative half-normal prior distribution is assigned to the standard deviation, d

    Hierarchical meta-analysis(HMA) model In the HMA model, we assume that indication-level parameters are fully exchangeable and vary according to a normal distribution: 2( , )ddNm  , where dm is the overall pooled effect 43 and d is the between-indication standard deviation. The pooled parameter dm is assigned a vague normal prior distribution and a weakl...

    work page 2003

  4. [4]

    Robert NJ, Diéras V , Glaspy J, et al. RIBBON-1: Randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol 2011; 29: 1252-1260. 20110307. DOI: 10.1200/jco.2010.28.0982

    work page doi:10.1200/jco.2010.28.0982 2011

  5. [5]

    Brufsky AM, Hurvitz S, Perez EA, et al. RIBBON-2: A randomized, double-blind, placebo- controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol 2011; 29: 4286-4293. 20111011. DOI: 10.12...

    work page doi:10.1200/jco.2010.34.1255 2011

  6. [6]

    Miles DW, Chan A, Dirix LY , et al. Phase III study of bevacizumab plus docetaxel compared with placebo plus docetaxel for the first-line treatment of human epidermal growth factor receptor 2– negative metastatic breast cancer. Journal of Clinical Oncology 2010; 28: 3239-3247. DOI: 10.1200/jco.2008.21.6457

    work page doi:10.1200/jco.2008.21.6457 2010

  7. [7]

    Biomarker results from the A V ADO phase 3 trial of first- line bevacizumab plus docetaxel for HER2-negative metastatic breast cancer

    Miles DW, de Haas SL, Dirix LY , et al. Biomarker results from the A V ADO phase 3 trial of first- line bevacizumab plus docetaxel for HER2-negative metastatic breast cancer. Br J Cancer 2013; 108: 1052-1060. 20130219. DOI: 10.1038/bjc.2013.69

    work page doi:10.1038/bjc.2013.69 2013

  8. [8]

    Gianni L, Romieu GH, Lichinitser M, et al. A VEREL: A randomized phase III trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer. J Clin Oncol 2013; 31: 1719-1725. 20130408. DOI: 10.1200/jco.2012.44.7912

    work page doi:10.1200/jco.2012.44.7912 2013

Show all 81 references
  1. [9]

    Sunitinib plus paclitaxel versus bevacizumab plus paclitaxel for first-line treatment of patients with advanced breast cancer: A phase III, randomized, open-label trial

    Robert NJ, Saleh MN, Paul D, et al. Sunitinib plus paclitaxel versus bevacizumab plus paclitaxel for first-line treatment of patients with advanced breast cancer: A phase III, randomized, open-label trial. Clin Breast Cancer 2011; 11: 82-92. 20110411. DOI: 10.1016/j.clbc.2011....

    2011 doi

  2. [10]

    Martín M, Roche H, Pinter T, et al. Motesanib, or open-label bevacizumab, in combination with paclitaxel, as first-line treatment for HER2-negative locally recurrent or metastatic breast cancer: A phase 2, randomised, double-blind, placebo-controlled study. Lancet Oncol 2011; ...

    2011 doi

  3. [11]

    Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer: the letrozole/fulvestrant and avastin (LEA) study

    Martín M, Loibl S, von Minckwitz G, et al. Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer: the letrozole/fulvestrant and avastin (LEA) study. J Clin Oncol 2015; 33: 1045-1052. 20150217. DOI: 10.120...

    2015 doi

  4. [12]

    Arteaga CL, Mayer IA, O'Neill AM, et al. A randomized phase III double-blinded placebo- controlled trial of first-line chemotherapy and trastuzumab with or without bevacizumab for patients with HER2/neu-overexpressing metastatic breast cancer (HER2+ MBC): A trial of the Easter...

    2012 doi

  5. [13]

    A Randomized Phase III Double-Blind Placebo-Controlled Trial of First-Line Chemotherapy and Trastuzumab With or Without Bevacizumab for Patients With HER-2/NEU Over-Expressing Metastatic Breast Cancer. 2007

    2007

  6. [15]

    Vrdoljak E, Marschner N, Zielinski C, et al. Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer. Ann Oncol 2016; 27: 2046-2052. 20160808. DOI: 10....

    2016 doi

  7. [16]

    Miles DW, Cameron D, Bondarenko I, et al. Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double- blind placebo-controlled randomised phase III trial with prospective biomarker evaluation...

    2017 doi

  8. [17]

    Improved survival with bevacizumab in advanced cervical cancer

    Tewari KS, Sill MW, Long HJr, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med 2014; 370: 734-743. DOI: 10.1056/NEJMoa1309748

    2014 doi

  9. [18]

    Tewari KS, Sill MW, Penson RT, et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial 69 (Gynecologic Oncology Group 240). Lancet 2017; 390: 1654-1663. 20170727. DOI: 10.1016/s01...

    2017 doi

  10. [19]

    Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer

    Kabbinavar FF, Hurwitz HI, Fehrenbacher L, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 2003; 21: 60-65. DOI: 10.1200/jco.2003.10.066

    2003 doi

  11. [20]

    Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial

    Kabbinavar FF, Schulz J, McCleod M, et al. Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol 2005; 23: 3697-3705. 20050228. DOI: 10.1200/jco.2005.05.112

    2005 doi

  12. [21]

    Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer

    Hurwitz HI, Fehrenbacher L, Novotny WF, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350: 2335-2342. DOI: 10.1056/NEJMoa032691

    2004 doi

  13. [22]

    Giantonio BJ, Catalano PJ, Meropol NJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007; 25: 1539-1...

    2007 doi

  14. [23]

    Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study

    Saltz LB, Clarke S, Díaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 2008; 26: 2013-2019. DOI: 10.1200/jco.2007.14.9930

    2008 doi

  15. [24]

    XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results

    Cassidy J, Clarke S, Díaz-Rubio E, et al. XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results. Br J Cancer 2011; 105: 58-64. 20110614. DOI: 10.1038/bjc.2011.201

    2011 doi

  16. [25]

    Tebbutt NC, Wilson K, Gebski VJ, et al. Capecitabine, Bevacizumab, and Mitomycin in First-Line Treatment of Metastatic Colorectal Cancer: Results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study. Journal of Clinical Oncology 2010; 28: 3191-3198....

    2010 doi

  17. [26]

    Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial

    Bennouna J, Sastre J, Arnold D, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 2013; 14: 29-37. 20121116. DOI: 10.1016/s1470-2045(12)70477-1

    2013 doi

  18. [27]

    Kubicka S, Greil R, André T, et al. Bevacizumab plus chemotherapy continued beyond first progression in patients with metastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings. Ann Oncol 2013; 24: 2342-2349. 201307...

    2013 doi

  19. [28]

    Schmoll H-J, Cunningham D, Sobrero A, et al. Cediranib with mFOLFOX6 versus bevacizumab with mFOLFOX6 as first-line treatment for patients with advanced colorectal cancer: A double-blind, randomized phase III study (HORIZON III). J Clin Oncol 2012; 30: 3588-3595. 20120910. DOI...

    2012 doi

  20. [29]

    Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (A VEX): an open- label, randomised phase 3 trial

    Cunningham D, Lang I, Marcuello E, et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (A VEX): an open- label, randomised phase 3 trial. Lancet Oncol 2013; 14: 1077-1085. 20130910. DOI: 10.1...

    2013 doi

  21. [30]

    Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial

    Guan Z-Z, Xu J-M, Luo R-C, et al. Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer: a randomized phase III ARTIST trial. Chin J Cancer 2011; 30: 682-689. DOI: 10.5732/cjc.011.10188

    2011 doi

  22. [31]

    A randomized trial of bevacizumab for newly diagnosed glioblastoma

    Gilbert MR, Dignam JJ, Armstrong TS, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 2014; 370: 699-708. DOI: 10.1056/NEJMoa1308573

    2014 doi

  23. [32]

    Sandmann T, Bourgon R, Garcia J, et al. Patients with proneural glioblastoma may derive overall survival benefit from the addition of bevacizumab to first-line radiotherapy and temozolomide: Retrospective analysis of the A V Aglio trial. J Clin Oncol 2015; 33: 2735-2744. 20150...

    2015 doi

  24. [33]

    EORTC 26101 phase III trial exploring the combination of bevacizumab and lomustine in patients with first progression of a glioblastoma

    Wick W, Brandes AA, Gorlia T, et al. EORTC 26101 phase III trial exploring the combination of bevacizumab and lomustine in patients with first progression of a glioblastoma. Journal of Clinical Oncology 2016; 34: 2001-2001. DOI: 10.1200/JCO.2016.34.15_suppl.2001

    2016 doi

  25. [34]

    Paclitaxel-carboplatin alone or with bevacizumab for non- small-cell lung cancer

    Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non- small-cell lung cancer. N Engl J Med 2006; 355: 2542-2550. DOI: 10.1056/NEJMoa061884

    2006 doi

  26. [35]

    Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: A V Ail

    Reck M, von Pawel J, Zatloukal P, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: A V Ail. J Clin Oncol 2009; 27: 1227-1234. 20090202. DOI: 10.1200/jco.2007.14.5466

    2009 doi

  27. [36]

    Reck M, von Pawel J, Zatloukal P, et al. Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: Results from a randomised phase III trial (A V AiL). Ann Oncol 2010; 21: 1804-1809. 20100211. DOI: ...

    2010 doi

  28. [37]

    Seto T, Kato T, Nishio M, et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): An open-label, randomised, multicentre, phase 2 study. Lancet Oncol 2014; 15: 1236-

    2014

  29. [38]

    Yamamoto N, Seto T, Nishio M, et al. Erlotinib plus bevacizumab vs erlotinib monotherapy as first-line treatment for advanced EGFR mutation-positive non-squamous non-small-cell lung cancer: Survival follow-up results of the randomized JO25567 study. Lung Cancer 2021; 151: 20-2...

    2021 doi

  30. [39]

    Zhou C, Wu Y-L, Chen G, et al. BEYOND: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study of First-Line Carboplatin/Paclitaxel Plus Bevacizumab or Placebo in Chinese Patients With Advanced or Recurrent Nonsquamous Non-Small-Cell Lung Cancer. J Clin On...

    2015 doi

  31. [40]

    Reck M, Mok TSK, Nishio M, et al. Atezolizumab plus bevacizumab and chemotherapy in non- small-cell lung cancer (IMpower150): Key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Lancet Respir Med 2019; 7: 387-

    2019

  32. [41]

    IMpower150 Final Overall Survival Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in First-Line Metastatic Nonsquamous NSCLC

    Socinski MA, Nishio M, Jotte RM, et al. IMpower150 Final Overall Survival Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in First-Line Metastatic Nonsquamous NSCLC. J Thorac Oncol 2021; 16: 1909-1924. 20210724. DOI: 10.1016/j.jtho.2021.07.009

    2021 doi

  33. [42]

    Saito H, Fukuhara T, Furuya N, et al. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): Interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol 2019; 20: 6...

    2019 doi

  34. [43]

    Kawashima Y , Fukuhara T, Saito H, et al. Bevacizumab plus erlotinib versus erlotinib alone in Japanese patients with advanced, metastatic, EGFR-mutant non-small-cell lung cancer (NEJ026): Overall survival analysis of an open-label, randomised, multicentre, phase 3 trial. Lanc...

    2022 doi

  35. [44]

    Incorporation of bevacizumab in the primary treatment of ovarian cancer

    Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011; 365: 2473-2483. DOI: 10.1056/NEJMoa1104390

    2011 doi

  36. [45]

    Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer

    Tewari KS, Burger RA, Enserro D, et al. Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer. J Clin Oncol 2019; 37: 2317-2328. 20190619. DOI: 10.1200/jco.19.01009

    2019 doi

  37. [46]

    A phase 3 trial of bevacizumab in ovarian cancer

    Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 2011; 365: 2484-2496. DOI: 10.1056/NEJMoa1103799

    2011 doi

  38. [47]

    Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): Overall survival results of a phase 3 randomised trial

    Oza AM, Cook AD, Pfisterer J, et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): Overall survival results of a phase 3 randomised trial. Lancet Oncol 2015; 16: 928-936. 20150623. DOI: 10.1016/s1470-2045(15)00086-8. 72

    2015 doi

  39. [48]

    Aghajanian C, Blank SV , Goff BA, et al. OCEANS: A randomized, double-blind, placebo- controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum- sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin ...

    2012 doi

  40. [49]

    Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer

    Aghajanian C, Goff BA, Nycum LR, et al. Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol 2015; 139: 10-16. 20150810. DOI: 10.1016/j.ygyn...

    2015 doi

  41. [50]

    Coleman RL, Brady MF, Herzog TJ, et al. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 tria...

    2017 doi

  42. [51]

    Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial

    Pujade-Lauraine E, Hilpert F, Weber B, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol 2014; 32: 1302-1308. 20140317. DOI: 10.1200/jco.2013.51.4489

    2014 doi

  43. [52]

    Bevacizumab with or after chemotherapy for platinum- resistant recurrent ovarian cancer: exploratory analyses of the AURELIA trial

    Bamias A, Gibbs E, Khoon Lee C, et al. Bevacizumab with or after chemotherapy for platinum- resistant recurrent ovarian cancer: exploratory analyses of the AURELIA trial. Ann Oncol 2017; 28: 1842-1848. DOI: 10.1093/annonc/mdx228

    2017 doi

  44. [53]

    Gore M, Hackshaw A, Brady WE, et al. An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor. Gynecol Oncol 2019; 153:...

    2019 doi

  45. [54]

    A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer

    Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 2003; 349: 427-434. DOI: 10.1056/NEJMoa021491

    2003 doi

  46. [55]

    von Minckwitz G, Puglisi F, Cortes J, et al. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an...

    2014 doi

  47. [59]

    Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240)

    Tewari KS, Sill MW, Penson RT, et al. Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240). Lancet 2017; 390: 1654-1663. 20170727. DOI: 10.1016/s0140-...

    2017 doi

  48. [62]

    Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer

    Hurwitz HI, Fehrenbacher L, Novotny WF, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350: 2335-

    2004

  49. [70]

    Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (A VEX): an open-label, randomised phase 3 trial

    Cunningham D, Lang I, Marcuello E, et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (A VEX): an open-label, randomised phase 3 trial. Lancet Oncol 2013; 14: 1077-1085. 20130910. DOI: 10.10...

    2013 doi

  50. [73]

    Sandmann T, Bourgon R, Garcia J, et al. Patients with proneural glioblastoma may derive overall survival benefit from the addition of bevacizumab to first-line radiotherapy and temozolomide: Retrospective analysis of the A V Aglio trial. J Clin Oncol 2015; 33: 2735-

    2015

  51. [81]

    Reck M, Mok TSK, Nishio M, et al. Atezolizumab plus bevacizumab and chemotherapy in non-small-cell lung cancer (IMpower150): Key subgroup analyses of patients with EGFR mutations or baseline liver metastases in a randomised, open-label phase 3 trial. Lancet Respir Med 2019; 7:...

    2019 doi

  52. [84]

    Kawashima Y , Fukuhara T, Saito H, et al. Bevacizumab plus erlotinib versus erlotinib alone in Japanese patients with advanced, metastatic, EGFR-mutant non-small-cell lung cancer (NEJ026): Overall survival analysis of an open-label, randomised, multicentre, phase 3 trial. Lanc...

    2022 doi

  53. [103]

    Randomized Phase III Trial of Gemcitabine and Cisplatin With Bevacizumab or Placebo in Patients With Advanced 30 Urothelial Carcinoma: Results of CALGB 90601 (Alliance)

    Rosenberg JE, Ballman KA, Halabi S, et al. Randomized Phase III Trial of Gemcitabine and Cisplatin With Bevacizumab or Placebo in Patients With Advanced 30 Urothelial Carcinoma: Results of CALGB 90601 (Alliance). J Clin Oncol 2021; 39: 2486-

    2021

  54. [106]

    On weakly informative prior distributions for the heterogeneity parameter in Bayesian random‐effects meta‐analysis

    Röver C, Bender R, Dias S, et al. On weakly informative prior distributions for the heterogeneity parameter in Bayesian random‐effects meta‐analysis. Research Synthesis Methods 2021; 12: 448-474. 31 Supplementary Material 32 A: Study identification and data extraction A-I: Ide...

    2005

  55. [107]

    Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer

    Miller KD, Chap LI, Holmes FA, et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol 2005; 23: 792-799. DOI: 10.1200/jco.2005.05.098

    2005 doi

  56. [108]

    Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer

    Miller KD, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. New England Journal of Medicine 2007; 357: 2666-2676. DOI: 10.1056/NEJMoa072113

    2007 doi

  57. [109]

    Bevacizumab in the first-line treatment of metastatic breast cancer

    Cameron D. Bevacizumab in the first-line treatment of metastatic breast cancer. European Journal of Cancer Supplements 2008; 6: 21-28. DOI: 10.1016/S1359-6349(08)70289-1

    2008 doi

  58. [115]

    Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206

    Rini BI, Halabi S, Rosenberg JE, et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol 2008; 26: 5422-5428. 20081020. DOI: 10.1200/jco.2008.16.9847

    2008 doi

  59. [116]

    Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206

    Rini BI, Halabi S, Rosenberg JE, et al. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J Clin Oncol 2010; 28: 2137-2143. 20100405. DOI: 10.1200/jco.2009.26.5561. 73

    2010 doi

  60. [117]

    Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial

    Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 2007; 370: 2103-

    2007

  61. [119]

    Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (A VOREN): final analysis of overall survival

    Escudier B, Bellmunt J, Négrier S, et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (A VOREN): final analysis of overall survival. J Clin Oncol 2010; 28: 2144-2150. 20100405. DOI: 10.1200/jco.2009.26.7849

    2010 doi

  62. [120]

    Shen L, Li J, Xu J, et al. Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer: Randomized, double-blind, phase III study (A V ATAR study). Gastric Cancer 2015; 18: 168-176. ...

    2015 doi

  63. [121]

    Bevacizumab in combination with chemotherapy as first- line therapy in advanced gastric cancer: A randomized, double-blind, placebo-controlled phase III study

    Ohtsu A, Shah MA, Van Cutsem E, et al. Bevacizumab in combination with chemotherapy as first- line therapy in advanced gastric cancer: A randomized, double-blind, placebo-controlled phase III study. J Clin Oncol 2011; 29: 3968-3976. 20110815. DOI: 10.1200/jco.2011.36.2236

    2011 doi

  64. [122]

    R-CHOP with or without bevacizumab in patients with previously untreated diffuse large B-cell lymphoma: Final MAIN study outcomes

    Seymour JF, Pfreundschuh M, Trnĕný M, et al. R-CHOP with or without bevacizumab in patients with previously untreated diffuse large B-cell lymphoma: Final MAIN study outcomes. Haematologica 2014; 99: 1343-1349. 20140603. DOI: 10.3324/haematol.2013.100818

    2014

  65. [123]

    Randomized Phase III Trial of Gemcitabine and Cisplatin With Bevacizumab or Placebo in Patients With Advanced Urothelial Carcinoma: Results of CALGB 90601 (Alliance)

    Rosenberg JE, Ballman KA, Halabi S, et al. Randomized Phase III Trial of Gemcitabine and Cisplatin With Bevacizumab or Placebo in Patients With Advanced Urothelial Carcinoma: Results of CALGB 90601 (Alliance). J Clin Oncol 2021; 39: 2486-2496. 20210514. DOI: 10.1200/jco.21.00286

    2021 doi

  66. [124]

    Kelly WK, Halabi S, Carducci M, et al. Randomized, Double-Blind, Placebo-Controlled Phase III Trial Comparing Docetaxel and Prednisone With or Without Bevacizumab in Men With Metastatic Castration-Resistant Prostate Cancer: CALGB 90401. Journal of Clinical Oncology 2012; 30: 1534-

    2012

  67. [126]

    Hensley ML, Miller A, O'Malley DM, et al. Randomized phase III trial of gemcitabine plus docetaxel plus bevacizumab or placebo as first-line treatment for metastatic uterine leiomyosarcoma: an NRG Oncology/Gynecologic Oncology Group study. J Clin Oncol 2015; 33: 1180-1185. 201...

    2015 doi

  68. [127]

    Bayesian methods in meta-analysis and evidence synthesis

    Sutton AJ and Abrams KR. Bayesian methods in meta-analysis and evidence synthesis. Statistical methods in medical research 2001; 10: 277-303

    2001

  69. [128]

    On weakly informative prior distributions for the heterogeneity parameter in Bayesian random‐effects meta‐analysis

    Röver C, Bender R, Dias S, et al. On weakly informative prior distributions for the heterogeneity parameter in Bayesian random‐effects meta‐analysis. Research Synthesis Methods 2021; 12: 448-474

    2021

  70. [401]

    DOI: 10.1016/s2213-2600(19)30084-0

    20190325. DOI: 10.1016/s2213-2600(19)30084-0

    doi

  71. [1244]

    DOI: 10.1016/s1470-2045(14)70381-x

    20140827. DOI: 10.1016/s1470-2045(14)70381-x. 71

    doi

  72. [1540]

    DOI: 10.1200/jco.2011.39.4767

    2011 doi

  73. [2111]

    DOI: 10.1016/s0140-6736(07)61904-7

    doi

Pith tools

Reviewed August 10, 2026 · model on record in the stance chip above.