Biomarker analyses in REGARD gastric/GEJ carcinoma patients
treated with VEGFR2-targeted antibody ramucirumab

J 2016

Biomarker analyses in REGARD gastric/GEJ carcinoma patients treated with VEGFR2-targeted antibody ramucirumab

FUCHS, Charles S., Josep TABERNERO, Jiří TOMÁŠEK, Ian CHAU, Bohuslav MELICHAR et. al.

Základní údaje

Originální název

Biomarker analyses in REGARD gastric/GEJ carcinoma patients treated with VEGFR2-targeted antibody ramucirumab

Autoři

FUCHS, Charles S. (840 Spojené státy), Josep TABERNERO (724 Španělsko), Jiří TOMÁŠEK (203 Česká republika, garant, domácí), Ian CHAU (826 Velká Británie a Severní Irsko), Bohuslav MELICHAR (203 Česká republika), Howard SAFRAN (840 Spojené státy), Mustapha A. TEHFE (124 Kanada), Dumitru FILIP (642 Rumunsko), Eldar TOPUZOV (643 Rusko), Luis SCHLITTLER (76 Brazílie), Anghel Adrian UDREA (642 Rumunsko), William CAMPBELL (320 Guatemala), Stephen BRINCAT (470 Malta), Michael EMIG (276 Německo), Symantha A. MELEMED (840 Spojené státy), Rebecca R. HOZAK (840 Spojené státy), David FERRY (840 Spojené státy), C. William CALDWELL (840 Spojené státy) a Jaffer A. AJANI (840 Spojené státy)

Vydání

British Journal of Cancer, London, Nature Publishing Group, 2016, 0007-0920

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.176

Kód RIV

RIV/00216224:14110/16:00092546

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1038/bjc.2016.293

UT WoS

000386474800012

Klíčová slova anglicky

ramucirumab; gastric carcinoma; gastroesophageal carcinoma; biomarkers; VEGFR2; antibody; angiogenesis; REGARD

Štítky

EL OK

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 3. 2017 10:15, Ing. Mgr. Věra Pospíšilíková

Anotace

V originále

Background: Angiogenesis inhibition is an important strategy for cancer treatment. Ramucirumab, a human IgG1 monoclonal antibody that targets VEGF receptor 2 (VEGFR2), inhibits VEGF-A, -C, -D binding and endothelial cell proliferation. To attempt to identify prognostic and predictive biomarkers, retrospective analyses were used to assess tumour (HER2, VEGFR2) and serum (VEGF-C and -D, and soluble (s) VEGFR1 and 3) biomarkers in phase 3 REGARD patients with metastatic gastric/gastroesophageal junction carcinoma. Methods: A total of 152 out of 355 (43%) patients randomised to ramucirumab or placebo had >= 1 evaluable biomarker result using VEGFR2 immunohistochemistry or HER2, immunohistochemistry or FISH, of blinded baseline tumour tissue samples. Serum samples (32 patients, 9%) were assayed for VEGF-C and -D, and sVEGFR1 and 3. Results: None of the biomarkers tested were associated with ramucirumab efficacy at a level of statistical significance. High VEGFR2 endothelial expression was associated with a non-significant prognostic trend toward shorter progression-free survival (high vs low HR=1.65, 95% CI = 0.84,3.23). Treatment with ramucirumab was associated with a trend toward improved survival in both high (HR=0.69, 95% CI = 0.38, 1.22) and low (HR = 0.73, 95% CI = 0.42, 1.26) VEGFR2 subgroups. The benefit associated with ramucirumab did not appear to differ by tumoural HER2 expression. Conclusions: REGARD exploratory analyses did not identify a strong potentially predictive biomarker of ramucirumab efficacy; however, statistical power was limited.

Citovat

FUCHS, Charles S., Josep TABERNERO, Jiří TOMÁŠEK, Ian CHAU, Bohuslav MELICHAR, Howard SAFRAN, Mustapha A. TEHFE, Dumitru FILIP, Eldar TOPUZOV, Luis SCHLITTLER, Anghel Adrian UDREA, William CAMPBELL, Stephen BRINCAT, Michael EMIG, Symantha A. MELEMED, Rebecca R. HOZAK, David FERRY, C. William CALDWELL a Jaffer A. AJANI. Biomarker analyses in REGARD gastric/GEJ carcinoma patients treated with VEGFR2-targeted antibody ramucirumab. British Journal of Cancer. London: Nature Publishing Group, 2016, roč. 115, č. 8, s. 974-982. ISSN 0007-0920. Dostupné z: https://dx.doi.org/10.1038/bjc.2016.293.

@article{1366019,
   author = {Fuchs, Charles S. and Tabernero, Josep and Tomášek, Jiří and Chau, Ian and Melichar, Bohuslav and Safran, Howard and Tehfe, Mustapha A. and Filip, Dumitru and Topuzov, Eldar and Schlittler, Luis and Udrea, Anghel Adrian and Campbell, William and Brincat, Stephen and Emig, Michael and Melemed, Symantha A. and Hozak, Rebecca R. and Ferry, David and Caldwell, C. William and Ajani, Jaffer A.},
   article_location = {London},
   article_number = {8},
   doi = {http://dx.doi.org/10.1038/bjc.2016.293},
   keywords = {ramucirumab; gastric carcinoma; gastroesophageal carcinoma; biomarkers; VEGFR2; antibody; angiogenesis; REGARD},
   language = {eng},
   issn = {0007-0920},
   journal = {British Journal of Cancer},
   title = {Biomarker analyses in REGARD gastric/GEJ carcinoma patients treated with VEGFR2-targeted antibody ramucirumab},
   url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061911/pdf/bjc2016293a.pdf},
   volume = {115},
   year = {2016}
}

TY  - JOUR
ID  - 1366019
AU  - Fuchs, Charles S. - Tabernero, Josep - Tomášek, Jiří - Chau, Ian - Melichar, Bohuslav - Safran, Howard - Tehfe, Mustapha A. - Filip, Dumitru - Topuzov, Eldar - Schlittler, Luis - Udrea, Anghel Adrian - Campbell, William - Brincat, Stephen - Emig, Michael - Melemed, Symantha A. - Hozak, Rebecca R. - Ferry, David - Caldwell, C. William - Ajani, Jaffer A.
PY  - 2016
TI  - Biomarker analyses in REGARD gastric/GEJ carcinoma patients treated with VEGFR2-targeted antibody ramucirumab
JF  - British Journal of Cancer
VL  - 115
IS  - 8
SP  - 974-982
EP  - 974-982
PB  - Nature Publishing Group
SN  - 00070920
KW  - ramucirumab
KW  - gastric carcinoma
KW  - gastroesophageal carcinoma
KW  - biomarkers
KW  - VEGFR2
KW  - antibody
KW  - angiogenesis
KW  - REGARD
UR  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061911/pdf/bjc2016293a.pdf
N2  - Background: Angiogenesis inhibition is an important strategy for cancer treatment. Ramucirumab, a human IgG1 monoclonal antibody that targets VEGF receptor 2 (VEGFR2), inhibits VEGF-A, -C, -D binding and endothelial cell proliferation. To attempt to identify prognostic and predictive biomarkers, retrospective analyses were used to assess tumour (HER2, VEGFR2) and serum (VEGF-C and -D, and soluble (s) VEGFR1 and 3) biomarkers in phase 3 REGARD patients with metastatic gastric/gastroesophageal junction carcinoma. Methods: A total of 152 out of 355 (43%) patients randomised to ramucirumab or placebo had >= 1 evaluable biomarker result using VEGFR2 immunohistochemistry or HER2, immunohistochemistry or FISH, of blinded baseline tumour tissue samples. Serum samples (32 patients, 9%) were assayed for VEGF-C and -D, and sVEGFR1 and 3. Results: None of the biomarkers tested were associated with ramucirumab efficacy at a level of statistical significance. High VEGFR2 endothelial expression was associated with a non-significant prognostic trend toward shorter progression-free survival (high vs low HR=1.65, 95% CI = 0.84,3.23). Treatment with ramucirumab was associated with a trend toward improved survival in both high (HR=0.69, 95% CI = 0.38, 1.22) and low (HR = 0.73, 95% CI = 0.42, 1.26) VEGFR2 subgroups. The benefit associated with ramucirumab did not appear to differ by tumoural HER2 expression. Conclusions: REGARD exploratory analyses did not identify a strong potentially predictive biomarker of ramucirumab efficacy; however, statistical power was limited.
ER  -

FUCHS, Charles S., Josep TABERNERO, Jiří TOMÁŠEK, Ian CHAU, Bohuslav MELICHAR, Howard SAFRAN, Mustapha A. TEHFE, Dumitru FILIP, Eldar TOPUZOV, Luis SCHLITTLER, Anghel Adrian UDREA, William CAMPBELL, Stephen BRINCAT, Michael EMIG, Symantha A. MELEMED, Rebecca R. HOZAK, David FERRY, C. William CALDWELL a Jaffer A. AJANI. Biomarker analyses in REGARD gastric/GEJ carcinoma patients treated with VEGFR2-targeted antibody ramucirumab. \textit{British Journal of Cancer}. London: Nature Publishing Group, 2016, roč.~115, č.~8, s.~974-982. ISSN~0007-0920. Dostupné z: https://dx.doi.org/10.1038/bjc.2016.293.

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