Creating a free account will enable you to subscribe to our daily and weekly email newsletters, as well as customize your reading experience to show only the categories most relevant to you.
Signing up only take a few minutes, so why not give it a try and see what you've been missing out on.
Adding the antibody therapy ramucirumab to the chemotherapy drug docetaxel did not delay disease progression for patients with HER2-negative, advanced breast cancer, according to results of a placebo-controlled, randomized, phase III clinical trial presented at the 2013 San Antonio Breast Cancer Symposium.
"Patients with metastatic or recurrent breast cancer, as well as those with locally advanced disease that cannot be surgically removed, have no curative options," said John R. Mackey, M.D., professor of oncology at the University of Alberta in Edmonton. "Standard cytotoxic chemotherapy is an option, but the efficacy of current treatments is modest and patients experience many adverse side effects.
"We had hoped that ramucirumab would give patients a new option for metastatic breast cancer. The outcome is disappointing, especially for the patients who participated on the trial and the many others suffering with this disease," added Mackey, who is also director of Translational Research in Oncology (TRIO). "Antiangiogenic agents have been successful in prolonging survival in a number of solid tumor types, including colon cancer and gastric cancer, but unfortunately, for reasons that we don't understand, they have not yet been shown to work for breast cancer."
"But we must work with the results that we have, and there were some patients on the trial who responded to treatment with ramucirumab," continued Mackey. "As a result, we will be conducting biomarker analyses to see if we can identify a subgroup of patients for whom the antibody therapy might be beneficial, but it will be a while before we have results."
For tumors to thrive, they need a good blood supply, and many tumors release factors that trigger nearby blood vessels to grow, a process called angiogenesis. Ramucirumab blocks angiogenesis by attaching to the protein on blood vessels that is key to the new blood vessel growth, vascular endothelial growth factor receptor 2 (VEGFR2). According to Mackey, other antiangiogenic therapies have not yielded great success in breast cancer but it had been hoped that ramucirumab would benefit patients because it is the only antiangiogenic antibody therapy to directly target VEGFR2.
Between August 2008 and December 2011, Mackey and colleagues enrolled 1,144 patients in the placebo-controlled, randomized, multinational, phase III clinical trial called the ramucirumab overall survival evaluation (ROSE) trial or the TRIO-12 trial. Patients were randomly assigned 1:2 to docetaxel plus placebo or docetaxel plus ramucirumab. To be eligible for the trial, patients had to have HER2-negative breast cancer that could not be removed surgically or HER2-negative, locally recurrent or metastatic breast cancer.
After a median follow-up of 16.2 months, progression-free survival was 9.5 months in the ramucirumab arm and 8.2 months in the control arm.
"The biggest positive that we can take from the trial is that we showed that a global academic group, TRIO, can successfully partner with industry to run a large, late-stage cancer clinical trial," said Mackey.
Title: Primary results of ROSE/TRIO-12, a randomized placebo controlled phase III trial evaluating the addition of ramucirumab to first-line docetaxel chemotherapy in metastatic breast cancer Publication Number: S5-04
Presenter: John R. Mackey, M.D.
Authors: John R Mackey1, Manuel Ramos-Vazquez2, Oleg Lipatov3, Nicole McCarthy4, Dimitry Kraznozhon5, Vladimir Semiglazov6, Alexey Manikhas7, Karen Gelmon8, Gottfried Konecny9, Marc Webster10, Roberto Hegg11, Sunil Verma12, Vera Gorbounova13, Dany Abi Gerges14, Francois Thireau15, Helena Fung15, Lorinda Simms16, Marc Buyse17, Ayman Ibrahim16 and Miguel Martin18. 1Cross Center Institute, Edmonton, Canada; 2Centro Oncologico de Galicia "José Antonio Quiroga y Pineiro", A Coruña, Spain; 3Republican Clinical Oncology Dispensary of Ministry of Health of Bashkortostan Republic, Ufa, Russian Federation; 4Haematology and Oncology Clinic Australia Wesley Medical Center, Queensland, Australia; 5Leningrad Regional Oncology Dispensary, Leningrad, Russian Federation; 6Institute of Oncology N.N. Petrov, St. Petersburg, Russian Federation; 7City Clinical Oncology Dispensary, St. Petersburg, Russian Federation; 8British Columbia Cancer Agency, Vancouver, Canada; 9University of California, Los Angeles; 10Tom Baker Cancer Centre, Calgary, Canada; 11Hospital Pérola Byigton Centro de Referência da Saúde da Mulher, Sao Paulo, Brazil; 12Sunnybrook Health Sciences Center, Toronto, Canada; 13N.N. Blokhin Russian Cancer Research Center of Russian Academy of Medical Sciences, Moscow, Russian Federation; 14Middle East Institute of Health, Bsalim, Lebanon; 15Translational Research in Oncology, Edmonton, Canada; 16ImClone Systems LLC, a Wholly Owned Subsidiary of Eli Lilly and Co., Bridgewater; 17International Drug Development Institute (IDDI), Louvain-la-Neuve, Belgium and 18Hospital General Universitario Gregorio Marañon, Madrid, Spain.
Background: To date, anti-angiogenic strategies in metastatic breast cancer have demonstrated benefits confined to modest improvements in progression-free survival, warranting evaluation of new agents in a placebo-controlled setting. Ramucirumab, an anti-VEGF receptor 2 antibody, is a human IgG1 antibody that specifically binds VEGF receptor 2 and blocks ligand stimulated activation. Early phase studies suggested anticancer effects in several solid tumors, and a phase III study demonstrated survival improvements in gastric cancer. The ROSE trial was designed to evaluate ramucirumab in the setting of HER2 negative, unresectable locally recurrent or metastatic breast cancer.
Methods: In this placebo-controlled randomized multinational phase III trial, patients with HER2 negative breast cancer who had not received cytotoxic chemotherapy in the advanced setting were randomized 1:2 to receive docetaxel 75 mg/m2 + placebo IV every three weeks, or to the same chemotherapy + ramucirumab 10 mg/kg IV every three weeks. Treatment was continued with each agent until investigator determined progressive disease using RECIST criteria, or until unacceptable toxicity. Patients were stratified by previous taxane therapy, visceral metastasis, hormone receptor status, and geographical region. An independent data monitoring committee oversaw the trial conduct, the efficacy database resides with TRIO, and this analysis was conducted by the TRIO statistical team in collaboration with Eli Lilly and Co. The primary endpoint was investigator-assessed PFS. The sample size was calculated to provide for this event-driven final PFS analysis and interim OS analysis, and a final OS analysis (to be conducted when at least 792 OS events are observed). ROSE also includes evaluation of potential predictive biomarkers.
Results: Between Aug 2008 and Dec 2011, 1144 patients were randomized. At data cut-off (March 31, 2013), median follow-up was 16.2 months. Safety, final PFS and interim OS results were presented. Anticipated data availability is early November 2013. Aggregated Patient Characteristics Age (years) 24 - 82 Prior Taxane Therapy (%) No 74 (%) Yes 26 Visceral Metastasis (%) No 29 Yes 71 Hormonal Receptor (%) Negative/Unknown 24 Positive 76 Geographic Region (%) Americas 24 Asia/Middle East/Africa 12 Europe/Australia/New Zealand 64
This study was funded by Eli Lilly and Company. Mackey declares no conflicts of interest.
Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our Breast Cancer category page for the latest news on this subject.
Please use one of the following formats to cite this article in your essay, paper or report:
American Association for Cancer Research. "Progression of advanced breast cancer not delayed by new combination therapy." Medical News Today. MediLexicon, Intl., 18 Dec. 2013. Web.
23 Apr. 2014. <http://www.medicalnewstoday.com/releases/270212>
American Association for Cancer Research. (2013, December 18). "Progression of advanced breast cancer not delayed by new combination therapy." Medical News Today. Retrieved from
Please note: If no author information is provided, the source is cited instead.
If you write about specific medications, operations, or procedures please do not name healthcare professionals by name.
For any corrections of factual information, or to contact our editorial team, please use our feedback form. Please send any medical news or health news press releases to:
Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.
This page was printed from: http://www.medicalnewstoday.com/releases/270212.php
Visit www.medicalnewstoday.com for medical news and health news headlines posted throughout the day, every day.
© 2004-2014 All rights reserved. MNT is the registered trade mark of MediLexicon International Limited.