Positive results from the Spanish National Cancer Research Centre (CNIO)’s first Phase 1 clinical trial of nintedanib may advance the therapeutic forward in studies to treat HER-2-negative breast cancer. A combination of nintedanib and standard chemotherapy (paclitaxel) provided remission to 50% of patients with the most common type of breast cancer who were treated with the joint therapy.
“The drug combination of paclitaxel and nintedanib has turned out to be a complete success, given that it is proved to be safe and that the pathologic complete response [rate of complete recovery] was 50%, which doubles the response compared to patients treated with standard therapy with paclitaxel,” said Miguel Ángel Quintela, head of CNIO’s Breast Cancer Clinical Research Unit, in a news release from CNIO.
These and other data were published in British Journal of Cancer under the title, “Phase I Clinical Trial of Nintedanib Plus Paclitaxel in Early HER-2-Negative Breast Cancer.” It was found that full-dose intensity was achievable, and the recommended dose to move forward to phase 2 trials is 150 mg. The toxic limit of drug was determined by transaminase liver enzymes.
As was revealed, the CNIO Breast Cancer Clinical Research Unit has launched a large-scale Phase 2 clinical trial to validate results in a sizable group of patients. Results and biomarker studies related to personalizing treatment to patients are expected by early 2015.
Nintedanib (Boehringer Ingelheim) may work against breast cancer by blocking angiogenesis, the growth of new blood vessels. Tumors require nutrients to thrive, and preventing blood vessel growth retards tumor growth rates. “Nintedanib is an improved antiangiogenic drug compared to previous angiogenesis inhibitors, given that it prevents angiogenesis in a more efficient way and with lower toxicity than its predecessors,” explained Dr. Quintela. Similar to other angiogenesis inhibitors, nintedanib blocks vascular endothelial growth factor receptors, but it also blocks platelet derived growth factor receptors and acts on fibroblast growth factor receptors.
Collaborations were vital to the success of this trial. CNIO worked with the Spanish National Health System and the Spanish Breast Cancer Research Group. Director of the Clinical Research Programme, oncologist Manuel Hidalgo, stated that “doing this type of study is critical to be able to test hypotheses formulated in the laboratory on patients without commercial pressures. These studies show that it is possible to create a network of research centers and hospitals to carry out clinical trials with a strong scientific component.”