Biomarkers in tissue from patients with upper gastrointestinal cancers treated with erlotinib and bevacizumab

Rohrberg, Kristoffer Staal; Pappot, Helle; Lassen, Ulrik; Westman, Maj; Olesen, René K; Pfeiffer, Per; Ladekarl, Morten; Sørensen, M.K.; Christensen, Ib Jarle; Skov, Birgit Guldhammer

doi:10.4161/cbt.11.8.14889

Cited by 7 publications

(10 citation statements)

References 35 publications

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“…The e cacy of bevacizumab-containing chemotherapy was investigated by stratifying patients into those with mDJA or mIA. In those with mIA, the OS in the Bevacizumab+ Platinum Group (51 months ) was signi cantly longer than that in the Platinum Group (17.5 months [12][13][14][15][16][17][18][19][20][21][22][23], P = 0.047; Supplemental Figure 2b), as previously reported. [15] We also found that in those with mDJA, both the PFS and OS in the Bevacizumab+ Platinum Group (15 months [1-] and 26 months [5-]) tended to be longer than those in the Platinum Group (7 [5][6][7][8][9] and 17 [8-22], P = 0.075 and P = 0.077; Supplemental Figure 2c and 2d, respectively).…”

Section: E Cacy Of Bevacizumab-containing Chemotherapy For Patients With Msbasupporting

confidence: 81%

“…Overman et al[16] reported that characterisation of VEGF-A expression has potential bene t for a VEGF-targeted therapeutic strategy in SBA. Rohrberg et al [17] reported that immunohistochemical expression of VEGF-A could be a biomarker for the e cacy of bevacizumab in upper gastrointestinal cancers, including metastatic gastric cancer (GC). The potential use of VEGF-A expression as a biomarker for the e cacy of bevacizumab for mDJA, however, has not yet been evaluated.…”

Section: Introductionmentioning

confidence: 99%

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Vascular Endothelial Growth Factor-A is an Immunohistochemical Biomarker for the Efficacy of Bevacizumab-containing Chemotherapy for Duodenal and Jejunal Adenocarcinoma

Amano

Iijima

Shinzaki

et al. 2021

Preprint

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Background: The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA.Methods: This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor A (VEGF-A), TP53, Ki67, β-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins.Results: A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30-0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression. Conclusion: Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.

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Section: E Cacy Of Bevacizumab-containing Chemotherapy For Patients With Msbasupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Vascular Endothelial Growth Factor-A is an Immunohistochemical Biomarker for the Efficacy of Bevacizumab-containing Chemotherapy for Duodenal and Jejunal Adenocarcinoma

Amano

Iijima

Shinzaki

et al. 2021

Preprint

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“…Identification of tumors most sensitive to therapy could improve therapeutic approaches and provide insight into mechanisms of resistance and further refine anti-angiogenic therapy [ 58 - 60 ]. In two phase II studies of bevacizumab, neuropilin- 2 mRNA significantly inversely correlated with PFS [ 17 ], while high VEGF-A correlated with longer OS and high VEGFR-2 correlated with shorter PFS [ 61 ].…”

Section: Resultsmentioning

confidence: 99%

Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review

Chen

Ryu

et al. 2017

Cancer Res Treat

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Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.

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“…More importantly, the development of biomarkers to select patients likely to benefit from targeted therapy cannot be over-emphasized. In a recent study, high VEGF expression was correlated to longer OS and high VEGFR-2 expression to shorter PFS in upper GI cancers treated with B + E, while EGFR expression and KRAS mutation status were not predictive [33]. Prospectively designed clinical trials with rigorous tissue sampling are desperately needed.…”

Section: Discussionmentioning

confidence: 99%

Phase II study of bevacizumab and erlotinib in the treatment of advanced hepatocellular carcinoma patients with sorafenib-refractory disease

et al. 2012

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SummaryBackground The combination of bevacizumab (B) and erlotinib (E) has shown promising clinical outcomes as the first-line treatment of advanced HCC patients. We aimed to evaluate the efficacy and safety of using combination of B + E in treating advanced HCC patients who had failed prior sorafenib treatment. Methods Eligible advanced HCC patients with documented radiological evidence of disease progression with sorafenib treatment were recruited. All patients received bevacizumab(B) at 10 mg/kg every 2 weeks with erlotinib(E) at 150 mg daily for a maximum of 6 cycles. Response assessments using both RECIST and modified RECIST criteria were performed after every 6 weeks. The primary endpoint was clinical benefit (CB) rate and a Simon two-stage design was employed. Results The trial was halted in the first stage according to the pre-set statistical criteria with 10 patients recruited. The median age was 47 years (range, 28–61) and all patients were in ECOG performance status 1. Eighty percent of patients were chronic hepatitis B carriers and all patients had Child A cirrhosis. Among these 10 patients, none of the enrolled patients achieved response or stable disease. The median time-to-progression was 1.81 months (95 % confidence interval [C.I.], 1.08–1.74 months) and overall survival was 4.37 months (95 % C.I., 1.08–11.66 months). Rash (70 %), diarrhea (50 %) and malaise (40 %) were the most commonly encountered toxicities. Conclusion The combination of B + E was well tolerated but had no activity in an unselected sorafenib-refractory advanced HCC population. Condensed abstract The combination of bevacizumab and erlotinib had no clinical activity in sorafenib-refractory HCC population.

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Biomarkers in tissue from patients with upper gastrointestinal cancers treated with erlotinib and bevacizumab

Cited by 7 publications

References 35 publications

Vascular Endothelial Growth Factor-A is an Immunohistochemical Biomarker for the Efficacy of Bevacizumab-containing Chemotherapy for Duodenal and Jejunal Adenocarcinoma

Vascular Endothelial Growth Factor-A is an Immunohistochemical Biomarker for the Efficacy of Bevacizumab-containing Chemotherapy for Duodenal and Jejunal Adenocarcinoma

Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review

Phase II study of bevacizumab and erlotinib in the treatment of advanced hepatocellular carcinoma patients with sorafenib-refractory disease

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