Title: LCZ 696 is superior to Valsartan in the prevention of cardiotoxity induced by trastuzumab, pertuzumab and Trastuzumab-DM1 monoclonal antibodies

Biography:

Nicola Maurea is the Chief of the Cardiology Department at the National Cancer Institute “IRCCS Fondazione Pascale” in Naples, Italy. He is one of the italian and international recognized leaders in the field of cardioncology and is President of the Italian Association of Cardioncology. He is Fellow of the European Society of Cardiology, American College of Cardiology and  National Association of Hospital Cardiologists (ANMCO). He is coauthor in numerous manuscripts on this topic in international journals and is regularly involved in national and international congresses and meetings as speaker or chairman.

Abstract

Cardiotoxic effects related to anticancer drugs are among the leading causes of morbidity and mortality in cancer patients treated with Trastuzumab (T), Pertuzumab (P) and Trastuzumab-DM1 (TDM1) [1-3]. Sacubitril-valsartan (LCZ 696), a drug used for the treatment of heart failure in patients with a reduced ejection fraction, is a combination drug, made up of neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan.

In this study, we aim to assess whether LCZ 696, administered during T, P or TDM1 treatment, reduces in vitro anticancer drugs-related cardiotoxicity, more efficiently respect to Valsartan (V). We used our in Vitro model, the H9C2 rat cardiomyoblasts, treated with 200 nM of T, P or TDM1 for 3 days, and then treated in the absence or presence of 10 µM of LCZ 696 or V for additional 3 days.

Our results show that LCZ 696 is superior respect to V in the reduction of the cardiotoxic effects of T, P and TDM1, when administered to cultures of H9C2 cardiomyoblasts after antineoplastic treatments.

Indeed, LCZ 696 was significantly more effective than V in reducing T related cardiotoxicity, increasing cell viability of 25 % more, respect to V (p<0.001). LCZ 696 is more strong in the reduction of P related toxicity, increasing cell viability of 35% more respect to V, with p<0.001. And finally, again more effective than V in reducing TDM1 toxicity, increasing cell viability of 10 % (p<0, 05).