The experimental drug nintedanib, combined with standard paclitaxel chemotherapy, led to a total remission of tumors in 50% of patients with early stage HER2-negative breast cancer, the most common type of breast cancer, according to a phase 1 clinical trial.
“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 [with] patients treated with standard therapy with paclitaxel,” said lead author Miguel Ángel Quintela, MD, of the Spanish National Cancer Research Centre (CNIO) in Madrid, Spain, and head of CNIO ́s Breast Cancer Clinical Research Unit. The trial was published in the British Journal of Cancer (2014; doi:10.1038/bjc.2014.397).
The trial included 10 patients with HER2-negative breast cancer, all of whom had early stage 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 personalized 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 tumors such as breast, colon, and lung cancer. The results, still in a preliminary stage, show that patients with the specific variant G2071A in the RET gene, which is a proto-oncogene or cancer driver gene, could be more sensitive to this drug.
Quintela said that if these data are confirmed, this genetic variant, which is present in 15% of white people, could be used as a reliable biomarker in personalized medicine to select patients best suited to receive this drug.
Recent theories suggest that a possible solution to cancer might be to ‘suffocate the tumor’ 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 tumor 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,” explained 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 from classic angiogenesis inhibitors.
FGFRs work in an aberrant manner in 10% to 15% of HER2-negative breast cancers, which could explain the compound’s greater antitumor activity compared with other compounds.