First clinical trial on HER-2-negative breast cancer with nintedanib shows promising results

By | September 11, 2014

According to Miguel Ángel Quintela, head of the Unit: “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.” The trial has also included 10 HER-2-negative breast cancer patients, all of them in early stages of the disease.

In light of the results, the CNIO Breast Cancer Clinical Research Unit has already launched a large-scale Phase II Clinical Trial to validate the results in a large group of patients. These results, including biomarker studies that will facilitate advances in personalised medicine, will be released by early 2015.

In parallel, the Unit has just completed a second Phase I Clinical Trial with a drug of the same family named dovitinib. The study has been tested in metastatic patients with different primary tumours such as breast, colon and lung cancer. The results, still in a preliminary stage, show that patients with a specific variant in the RET gene -a proto-oncogene or cancer driver gene; variant G2071A- could be more sensitive to this drug. This work has been published by Molecular Oncology.

As Quintela says, if these data are confirmed, this genetic variant -present in 15% of Caucasian people- could be used as a reliable biomarker in personalised medicine to select the best suited candidates to receive this drug.

‘Suffocate’ the Tumour to Fight It

Recent theories suggest that a possible solution to cancer might be to ‘suffocate the tumour’ by blocking the formation of new blood vessels that surround it.

The mechanism of action of the experimental drugs nintedanib (Boehringer Ingelheim) and dovitinib (Novartis) precisely consists on blocking the formation of new blood vessels, so-called angiogenesis, which can lead to retardation in tumour growth rates and limit its viability.

“Nintedanib [a drug that there is more experimental data on] 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,” explains Quintela.

Nintedanib, in addition to blocking vascular endothelial growth factor receptors (VEGFR) and platelet derived growth factor receptors (PDGFR), also acts on fibroblast growth factor receptors (FGFR), which makes it different to classical angiogenesis inhibitors.

FGFRs work in an aberrant manner in 10-15% of HER-2 negative breast cancers, which could explain a greater the compound’s greater anti- tumour activity compared to other compounds.

source : http://www.sciencedaily.com/releases/2014/09/140910120424.htm