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 open-label, randomised phase 3 trial

Minckwitz, Gϋnter von; Puglisi, Fabio; Cortés, Javier; Vrdoljak, Eduard; Marschner, Norbert; Zielinski, Christoph; Villanueva, Cristian; Romieu, Gilles; Láng, István; Ciruelos, Eva; Laurentiis, Michelino De; Veyret, Corinne; Ducla, Sabine de; Freudensprung, Ulrich; Srock, Stefanie; Gligorov, J.

doi:10.1016/s1470-2045(14)70439-5

Cited by 119 publications

(119 citation statements)

References 20 publications

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“…These results suggested that, especially in high-risk patients, it might be beneficial to further extend the treatment duration of bevacizumab beyond chemotherapy and even after disease progression. Therefore, ongoing trials (NCT01462890 and NCT01802749; https://clinicaltrials.gov/) are addressing these important questions in ovarian cancer, whereas studies in colorectal and breast cancer already provided evidence of benefit (43,44).…”

Section: Discussionmentioning

confidence: 99%

FAK regulates platelet extravasation and tumor growth after antiangiogenic therapy withdrawal

Haemmerle¹,

Bottsford-Miller²,

Pradeep³

et al. 2016

Journal of Clinical Investigation

103

101

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Section: Discussionmentioning

confidence: 99%

FAK regulates platelet extravasation and tumor growth after antiangiogenic therapy withdrawal

Haemmerle¹,

Bottsford-Miller²,

Pradeep³

et al. 2016

Journal of Clinical Investigation

103

101

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“…Recent results with ramucirumab plus docetaxel in the ROSE/TRIO trial in advanced HER2-negative breast cancer were disappointing [34].Nomeaningful improvementin importantclinical outcomes such as OS versus docetaxel alone were observed, and there was significantly more toxicity [34]. However, results from the TANIA and IMELDA trials in this indication demonstrated that continued second-line treatment with bevacizumab plus chemotherapy significantly improved PFS compared with bevacizumab alone [143,144]. It is clear that the use of antiangiogenic therapy in breast cancer remains to be fully evaluated [17].…”

Section: Wwwtheoncologistcom ©Alphamed Press 2015mentioning

confidence: 99%

Targeting Angiogenesis in Cancer Therapy: Moving Beyond Vascular Endothelial Growth Factor

2015

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Angiogenesis, or the formation of new capillary blood vessels, occurs primarily during human development and reproduction; however, aberrant regulation of angiogenesis is also a fundamental process found in several pathologic conditions, including cancer. As a process required for invasion and metastasis, tumor angiogenesis constitutes an important point of control of cancer progression. Although not yet completely understood, the complex process of tumor angiogenesis involves highly regulated orchestration of multiple signaling pathways. The proangiogenic signaling molecule vascular endothelial growth factor (VEGF) and its cognate receptor (VEGF receptor 2 [VEGFR‐2]) play a central role in angiogenesis and often are highly expressed in human cancers, and initial clinical efforts to develop antiangiogenic treatments focused largely on inhibiting VEGF/VEGFR signaling. Such approaches, however, often lead to transient responses and further disease progression because angiogenesis is regulated by multiple pathways that are able to compensate for each other when single pathways are inhibited. The platelet‐derived growth factor (PDGF) and PDGF receptor (PDGFR) and fibroblast growth factor (FGF) and FGF receptor (FGFR) pathways, for example, provide potential escape mechanisms from anti‐VEGF/VEGFR therapy that could facilitate resumption of tumor growth. Accordingly, more recent treatments have focused on inhibiting multiple signaling pathways simultaneously. This comprehensive review discusses the limitations of inhibiting VEGF signaling alone as an antiangiogenic strategy, the importance of other angiogenic pathways including PDGF/PDGFR and FGF/FGFR, and the novel current and emerging agents that target multiple angiogenic pathways for the treatment of advanced solid tumors. Implications for Practice: Significant advances in cancer treatment have been achieved with the development of antiangiogenic agents, the majority of which have focused on inhibition of the vascular endothelial growth factor (VEGF) pathway. VEGF targeting alone, however, has not proven to be as efficacious as originally hoped, and it is increasingly clear that there are many interconnected and compensatory pathways that can overcome VEGF‐targeted inhibition of angiogenesis. Maximizing the potential of antiangiogenic therapy is likely to require a broader therapeutic approach using a new generation of multitargeted antiangiogenic agents.

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“…More recently, however, there has been renewed interest in reconsidering bevacizumab for the treatment of breast cancer based on several phase III clinical trial results, including one in the neoadjuvant and adjuvant setting (NSABP-B40) and two in the maintenance metastatic setting (IMELDA and TANIA; refs. [3][4][5]. Importantly, a number of trial results and meta-analyses suggest the extent of beneficial effect (and associated toxicities) of adding bevacizumab to chemotherapy may depend on the concurrent chemotherapy regimen used (2,4,6,7).…”

Section: Introductionmentioning

confidence: 99%

Preclinical Efficacy of Bevacizumab with CRLX101, an Investigational Nanoparticle–Drug Conjugate, in Treatment of Metastatic Triple-Negative Breast Cancer

et al. 2016

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VEGF pathway-targeting antiangiogenic drugs, such as bevacizumab, when combined with chemotherapy have changed clinical practice for the treatment of a broad spectrum of human cancers. However, adaptive resistance often develops, and one major mechanism is elevated tumor hypoxia and upregulated hypoxia-inducible factor-1a (HIF1a) caused by antiangiogenic treatment. Reduced tumor vessel numbers and function following antiangiogenic therapy may also affect intratumoral delivery of concurrently administered chemotherapy. Nonetheless, combining chemotherapy and bevacizumab can lead to improved response rates, progression-free survival, and sometimes, overall survival, the extent of which can partly depend on the chemotherapy backbone. A rational, complementing chemotherapy partner for combination with bevacizumab would not only reduce HIF1a to overcome hypoxia-induced resistance, but also improve tumor perfusion to maintain intratumoral drug delivery. Here, we evaluated bevacizumab and CRLX101, an investigational nanoparticle-drug conjugate containing camptothecin, in preclinical mouse models of orthotopic primary triple-negative breast tumor xenografts, including a patient-derived xenograft. We also evaluated long-term efficacy of CRLX101 and bevacizumab to treat postsurgical, advanced metastatic breast cancer in mice. CRLX101 alone and combined with bevacizumab was highly efficacious, leading to complete tumor regressions, reduced metastasis, and greatly extended survival of mice with metastatic disease. Moreover, CRLX101 led to improved tumor perfusion and reduced hypoxia, as measured by contrast-enhanced ultrasound and photoacoustic imaging. CRLX101 durably suppressed HIF1a, thus potentially counteracting undesirable effects of elevated tumor hypoxia caused by bevacizumab. Our preclinical results show pairing a potent cytotoxic nanoparticle chemotherapeutic that complements and improves concurrent antiangiogenic therapy may be a promising treatment strategy for metastatic breast cancer. Cancer Res; 76(15); 4493-503. Ó2016 AACR.

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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 open-label, randomised phase 3 trial

Cited by 119 publications

References 20 publications

FAK regulates platelet extravasation and tumor growth after antiangiogenic therapy withdrawal

FAK regulates platelet extravasation and tumor growth after antiangiogenic therapy withdrawal

Targeting Angiogenesis in Cancer Therapy: Moving Beyond Vascular Endothelial Growth Factor

Preclinical Efficacy of Bevacizumab with CRLX101, an Investigational Nanoparticle–Drug Conjugate, in Treatment of Metastatic Triple-Negative Breast Cancer

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