SynthesisFrontiers in oncology2026
The efficacy of angiogenesis inhibitors combined with chemotherapy in advanced breast cancer: a systematic review and meta-analysis.
Synthesis in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.
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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.
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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.
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Corrections and comments
- Erratum issued
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clinical trial registration: Globally, breast cancer is the most common malignancy in women. Despite treatment advances, 20-30% of early-stage patients progress to advanced disease, which remains largely incurable with a 5-year survival rate of only ~20%. Chemotherapy, the current mainstay, has reached a therapeutic plateau, with limited efficacy and potential pro-metastatic effects. Anti-angiogenic agents targeting VEGF/VEGFR2 (e.g., bevacizumab, TKIs) are used clinically, but their benefit in advanced breast cancer is controversial: progression-free survival (PFS) gains are inconsistent, overall survival (OS) benefits are unclear, and resistance with class-specific toxicities (e.g., hypertension) is common. Furthermore, comparative efficacy across drug classes and optimal patient selection remain undefined. These unresolved issues highlight the urgent need for a comprehensive synthesis to guide clinical decisions and future research. Methods: Systematic search of PubMed/Web of Science (up to July 16, 2025) identified 29 phase II/III RCTs (N = 8,480) comparing angiogenesis inhibitors + chemotherapy vs. chemotherapy alone (± placebo) in advanced breast cancer. Outcomes included PFS, OS, objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety. Two independent reviewers performed screening, extraction, and quality assessment. Pooled HRs (95% CI) for PFS/OS; ORs for binary outcomes. Random-effects model used if I² ≥ 50%; prespecified subgroup/sensitivity analyses explored heterogeneity. Results: This meta-analysis (29 RCTs, N = 11,068) showed that adding angiogenesis inhibitors in advanced breast cancer significantly improved PFS (HR 0.75), ORR, CBR, and DCR (all P<0.001), but not OS (HR 0.95, P = 0.171). PFS benefit varied by subtype: mAbs (e.g., bevacizumab) outperformed TKIs in TNBC (HR 0.59 vs. 0.75); TKIs trended better in HR+ disease (HR 0.67). Benefit was consistent across metastasis patterns but greater in patients without bone metastasis. Safety risks increased significantly, including hypertension (OR 4.59), thrombocytopenia (OR 4.54), proteinuria (OR 2.38), hand-foot syndrome (OR 2.14), and diarrhea (OR 1.97). Conclusions: This meta-analysis (29 RCTs) finds that adding angiogenesis inhibitors to chemotherapy significantly improves PFS and response in advanced breast cancer-especially in TNBC with mAbs and HR+ disease with TKIs-but not OS. Benefit is independent of visceral metastasis but reduced in bone metastases. Increased toxicities (hypertension, proteinuria, hand-foot syndrome, diarrhea) warrant proactive management.
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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.