Dr. Yadav on Olaparib/Neratinib in HER2-Overexpressing Uterine Serous Carcinoma

Ghanshyam Yadav, MD, first-year resident, Baylor College of Medicine, discusses the combination of olaparib (Lynparza) and neratinib (Nerlyx) in patients with HER2-overexpressing uterine serous carcinoma.

Uterine serous carcinoma is highly resistant to chemotherapy, says Yadav. A lot of research is examining cell-surface targeting. Much of the research Yadav has done has involved using TKIs in uterine serous cancers. Yadav and colleagues hypothesized that combining a TKI, which targets the ERBB2 pathway, with olaparib, which targets the DNA damage repair pathway, could have synergistic activity in this patient population.

Treatment with a PARP inhibitor was found to increase the HER2 expression on the surface of the cells, providing more of a target for neratinib, explains Yadav. Moreover, cells that had been treated with neratinib increased the active component of PARP. In the mouse study, the combination proved to be synergistic with significantly longer survival benefit and a statistically significant difference in tumor growth in one of the cell lines, says Yadav.