Phase II Trial of the Combination of Bevacizumab and Erlotinib in Patients Who Have Advanced Hepatocellular Carcinoma

Thomas, Melanie B.; Morris, Jeffrey S.; Chadha, Romil; Iwasaki, Michiko; Kaur, Harmeet; Lin, Elinor; Kaseb, Ahmed O.; Glover, Katrina Y.; Davila, Marta; Abbruzzese, James L.

doi:10.1200/jco.2008.18.3301

Cited by 329 publications

(252 citation statements)

References 44 publications

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“…A second approach is to combine MTT targeting different molecular pathways. Preliminary results of a phase II trial combining bevacizumab with erlotinib showed a response rate of 20% and a median overall survival of 15.5 months [390]. However, these preliminary results must be validated by larger randomized trials.…”

Section: Future Directionsmentioning

confidence: 99%

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

et al. 2010

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Introduction The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on the management of hepatocellular carcinoma (HCC) in December 2008 to develop consensus recommendations. Methods The working party consisted of expert hepatologist, hepatobiliary surgeon, radiologist, and oncologist from Asian-Pacific region, who were requested to make drafts prior to the consensus meeting held at Bali, Indonesia on 4 December 2008. The quality of existing evidence and strength of recommendations were ranked from 1 (highest) to 5 (lowest) and from A (strongest) to D (weakest), respectively, according to the Oxford system of evidence-based approach for developing the consensus statements. 123Hepatol Int (2010) 4: 439-474 DOI 10.1007/s12072-010-9165-7 Results Participants of the consensus meeting assessed the quality of cited studies and assigned grades to the recommendation statements. Finalized recommendations were presented at the fourth APASL single topic conference on viral-related HCC at Bali, Indonesia and approved by the participants of the conference.

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Section: Future Directionsmentioning

confidence: 99%

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

et al. 2010

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“…Although VEGFRs were postulated as mediators of sorafenib response in HCC, testing for VEGF-A serum levels was not found to be predictive of sorafenib treatment success ( 10 ). Moreover, bevacizumab, an antibody against VEGF-A, only shows minimal responses in HCC (17)(18)(19)(20). A possible explanation for this is that the mechanism of action of sorafenib is predominantly independent of VEGF-A inhibition.…”

Section: Introductionmentioning

confidence: 99%

Human and Mouse VEGFA-Amplified Hepatocellular Carcinomas Are Highly Sensitive to Sorafenib Treatment

et al. 2014

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Death rates from hepatocellular carcinoma (HCC) are steadily increasing, yet therapeutic options for advanced HCC are limited. We identify a subset of mouse and human HCCs harboring VEGFA genomic amplifi cation, displaying distinct biologic characteristics. Unlike common tumor amplifi cations, this one seems to work via heterotypic paracrine interactions; stromal VEGF receptors (VEGFR), responding to tumor VEGF-A, produce hepatocyte growth factor (HGF) that reciprocally affects tumor cells. VEGF-A inhibition results in HGF downregulation and reduced proliferation, specifi cally in amplicon-positive mouse HCCs. Sorafenib-the fi rst-line drug in advanced HCC-targets multiple kinases, including VEGFRs, but has only an overall mild benefi cial effect. We found that VEGFA amplifi cation specifi es mouse and human HCCs that are distinctly sensitive to sorafenib. FISH analysis of a retrospective patient cohort showed markedly improved survival of sorafenib-treated patients with VEGFA -amplifi ed HCCs, suggesting that VEGFA amplifi cation is a potential biomarker for HCC response to VEGF-A-blocking drugs. SIGNIFICANCE:Using a mouse model of infl ammation-driven cancer, we identifi ed a subclass of HCC carrying VEGFA amplifi cation, which is particularly sensitive to VEGF-A inhibition. We found that a similar amplifi cation in human HCC identifi es patients who favorably responded to sorafenib-the fi rst-line treatment of advanced HCC-which has an overall moderate therapeutic effi cacy. Cancer Discov; 4(6);

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“…Partial responses have been observed in patients after bevacizumab monotherapy and disease stabilisation in 30% of treated patients has been documented (Siegel et al, 2008). Combination treatment of bevacizumab with EGFR targeting agents was shown to be safe and revealed promising initial results with a median time to progression of 9 months (Thomas et al, 2007b) (see Table 1). Overall, bevacizumab has shown promising results as a single agent as well as in combination with other targeted therapies and cytotoxic therapy (Zhu et al, 2006) supporting the idea of a vascular targeting therapy for the treatment of HCC.…”

Section: Results From Phase I and Ii Studies Testing Other Approved Tmentioning

confidence: 99%

Molecular therapy for the treatment of hepatocellular carcinoma

et al. 2008

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Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Conventional cytotoxic chemotherapy has failed to show a substantial benefit for patients with HCC. Recently, a number of new drugs targeting molecular mechanisms involved in liver cell transformation have entered into clinical trials and led to encouraging results. In this review we summarise this data and point to a number of new compounds, which are currently being tested and can potentially broaden our therapeutic arsenal even further.

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Phase II Trial of the Combination of Bevacizumab and Erlotinib in Patients Who Have Advanced Hepatocellular Carcinoma

Abstract: The combination of B + E in patients who had advanced HCC showed significant, clinically meaningful antitumor activity. B + E warrant additional evaluation in randomized controlled trials.

Cited by 329 publications

References 44 publications

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

Human and Mouse VEGFA-Amplified Hepatocellular Carcinomas Are Highly Sensitive to Sorafenib Treatment

Molecular therapy for the treatment of hepatocellular carcinoma

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