Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial

Imagem de Miniatura
Arquivos
art_ZHU_Ramucirumab_versus_placebo_as_secondline_treatment_in_patients_2015.PDF (515.78 KB)
Citações na Scopus
668
Tipo de produção
article
Data de publicação
2015
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER SCIENCE INC
Autores
ZHU, Andrew X.
PARK, Joon Oh
RYOO, Baek-Yeol
YEN, Chia-Jui
POON, Ronnie
PASTORELLI, Davide
BLANC, Jean-Frederic
CHUNG, Hyun Cheol
BARON, Ari D.
Citação
LANCET ONCOLOGY, v.16, n.7, p.859-870, 2015
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background VEGF and VEGF receptor-2-mediated angiogenesis contribute to hepatocellular carcinoma pathogenesis. Ramucirumab is a recombinant IgG1 monoclonal antibody and VEGF receptor-2 antagonist. We aimed to assess the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma following first-line therapy with sorafenib. Methods In this randomised, placebo-controlled, double-blind, multicentre, phase 3 trial (REACH), patients were enrolled from 154 centres in 27 countries. Eligible patients were aged 18 years or older, had hepatocellular carcinoma with Barcelona Clinic Liver Cancer stage C disease or stage B disease that was refractory or not amenable to locoregional therapy, had Child-Pugh A liver disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, had previously received sorafenib (stopped because of progression or intolerance), and had adequate haematological and biochemical parameters. Patients were randomly assigned (1:1) to receive intravenous ramucirumab (8 mg/kg) or placebo every 2 weeks, plus best supportive care, until disease progression, unacceptable toxicity, or death. Randomisation was stratified by geographic region and cause of liver disease with a stratified permuted block method. Patients, medical staff, investigators, and the funder were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01140347. Findings Between Nov 4, 2010, and April 18, 2013, 565 patients were enrolled, of whom 283 were assigned to ramucirumab and 282 were assigned to placebo. Median overall survival for the ramucirumab group was 9.2 months (95% CI 8.0-10.6) versus 7.6 months (6.0-9.3) for the placebo group (HR 0.87 [95% CI 0.72-1.05]; p=0.14). Grade 3 or greater adverse events occurring in 5% or more of patients in either treatment group were ascites (13 [5%] of 277 patients treated with ramucirumab vs 11 [4%] of 276 patients treated with placebo), hypertension (34 [12%] vs ten [4%]), asthenia (14 [5%] vs five [2%]), malignant neoplasm progression (18 [6%] vs 11 [4%]), increased aspartate aminotransferase concentration (15 [5%] vs 23 [8%]), thrombocytopenia (13 [5%] vs one [<1%]), hyperbilirubinaemia (three [1%] vs 13 [5%]), and increased blood bilirubin (five [2%] vs 14 [5%]). The most frequently reported (>= 1%) treatment-emergent serious adverse event of any grade or grade 3 or more was malignant neoplasm progression. Interpretation Second-line treatment with ramucirumab did not significantly improve survival over placebo in patients with advanced hepatocellular carcinoma. No new safety signals were noted in eligible patients and the safety profile is manageable.
Palavras-chave
URI
https://observatorio.fm.usp.br/handle/OPI/11879
Referências
  1. Amini A, 2012, CURR CANCER DRUG TAR, V12, P23
  2. CASTELLS L, 1995, LIVER, V15, P159
  3. Cheng AL, 2009, LANCET ONCOL, V10, P25, DOI 10.1016/S1470-2045(08)70285-7
  4. Chiu J, 2012, CANCER-AM CANCER SOC, V118, P5293, DOI 10.1002/cncr.27543
  5. Ferlay J, 2015, INT J CANCER, V136, pE356
  6. Fuchs CS, 2014, LANCET, V383, P31, DOI 10.1016/S0140-6736(13)61719-5
  7. Garcia JA, 2014, CANCER-AM CANCER SOC, V120, P1647, DOI 10.1002/cncr.28634
  8. Gomaa AI, 2009, WORLD J GASTROENTERO, V15, P1301, DOI 10.3748/wjg.15.1301
  9. Hoshida Y, 2009, CANCER RES, V69, P7385, DOI 10.1158/0008-5472.CAN-09-1089
  10. Huang JF, 2011, J CLIN PATHOL, V64, P343, DOI 10.1136/jcp.2010.085142
  11. Iavarone M, 2015, HEPATOLOGY, V62, P784, DOI 10.1002/hep.27729
  12. Kelley RK, 2013, J CLIN ONCOL, V31, P3483, DOI 10.1200/JCO.2013.49.7941
  13. Kim JE, 2011, CANCER CHEMOTH PHARM, V68, P1285, DOI 10.1007/s00280-011-1616-x
  14. Lencioni R, 2014, INT J CLIN PRACT, V68, P609, DOI 10.1111/ijcp.12352
  15. Llovet JM, 2014, CLIN CANCER RES, V20, P2072, DOI 10.1158/1078-0432.CCR-13-0547
  16. Llovet JM, 2008, NEW ENGL J MED, V359, P378, DOI 10.1056/NEJMoa0708857
  17. Mailey B, 2011, ARCH SURG-CHICAGO, V146, P26, DOI 10.1001/archsurg.2010.295
  18. Pons Fernando, 2005, HPB (Oxford), V7, P35, DOI 10.1080/13651820410024058
  19. Reig M, 2013, HEPATOLOGY, V58, P2023, DOI 10.1002/hep.26586
  20. Shan YF, 2011, MED ONCOL, V28, P1012, DOI 10.1007/s12032-010-9600-6
  21. Spratlin JL, 2010, J CLIN ONCOL, V28, P780, DOI 10.1200/JCO.2009.23.7537
  22. Sullivan LA, 2010, MABS-AUSTIN, V2, P165
  23. Tangkijvanich P, 2000, J CLIN GASTROENTEROL, V31, P302, DOI 10.1097/00004836-200012000-00007
  24. Manghisi G, 1998, HEPATOLOGY, V28, P751
  25. Tugues S, 2011, MOL ASPECTS MED, V32, P88, DOI 10.1016/j.mam.2011.04.004
  26. Yamashita T, 2008, CANCER RES, V68, P1451, DOI 10.1158/0008-5472.CAN-07-6013
  27. Zhang XF, 2009, EJSO-EUR J SURG ONC, V35, P622, DOI 10.1016/j.ejso.2008.08.003
  28. Zhu AX, 2014, ANN ONCOL, V25, P1
  29. Zhu AX, 2015, P AM SOC CLIN ONCOL, V33
  30. Zhu AX, 2013, CLIN CANCER RES, V19, P6614, DOI 10.1158/1078-0432.CCR-13-1442
  31. Zhu AX, 2011, NAT REV CLIN ONCOL, V8, P292, DOI 10.1038/nrclinonc.2011.30

Coleções
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - ODS/03