Abstract 3157: Cyclin E1 overexpression identifies patients with greater benefit from bevacizumab in platinum sensitive recurrent ovarian cancer
Authors: Ribeiro Adriana Regina G. , Salvadori Marcella M. , Brot Louise de , Bovolim Graziele , Mantoan Henrique , Ilelis Felipe , Alves Mariana R. , Amaral Nayra Soares , Sanches Solange M. , Lisboa Joyce , Santos Elizabeth S. dos , Pereira Ronaldo , Castro Fabricio S. , Lima Joao Paulo S. , Guimaraes Andrea P. , Baiocchi Glauco , Costa Alexandre Andre B. Da 
Published: August 2019

Abstract
Introduction: Bevacizumab is an antiangiogenic agent approved to treat ovarian cancer in combination to chemotherapy. The relative benefit of bevacizumab in ovarian cancer patients seems to be greater the more the disease becomes platinum resistant. Cyclin E1 overexpression is a marker of platinum resistance. In this study we aimed to evaluate the benefit of bevacizumab in platinum sensitive recurrent ovarian cancer and to test if the benefit changes according to platinum-free interval (PFI) and cyclin E1 expression.
Methods: We retrospectively evaluated data from patients with platinum sensitive recurrent ovarian cancer treated with CT plus bevacizumab (Bev group) and CT alone (CT group) at a tertiary cancer center in Brazil from 2005 to 2017. The two groups were paired according to histology, platinum free interval and number of previous treatment lines. Cyclin E1 expression was evaluated by immunohistochemistry in tissue microarray. Progression-free survival (PFS) was compared between the groups with log rank test and cox regression.
Results: 124 patients were included, 62 in each group. Bev group and CT group were well balanced regarding histology (high grade serous carcinoma 94% in Bev group, 93% in CT group), PFI (PFI &gt; 12 months in 36.2% in Bev group, 39.3% in CT group) and number of previous treatment lines (one previous chemotherapy in 55.7% in Bev group, 60.0% in CT group). Median age and median PFI were 56.2 years old and 59.2 years old, and 9.7 months and 10.5 months, in the Bev and CT groups, respectively. All patients were treated with platinum doublets with paclitaxel, gemcitabine or liposomal doxorubicin except for one patient treated with cisplatin plus bevacizumab and one patient treated with liposomal doxorubicin. Median PFS (mPFS) was 19.5 months for the Bev group vs. 16.0 months in the CT group (p = 0.150). Patients with a PFI &gt; 12 months showed a mPFS of 20.0 months vs. 15.5 for patients with a PFI &lt; 12 months (p=0.029). Patients with cyclin E1 overexpression showed a mPFS of 15.8 months vs. 19.7 months for those without cyclin E1 overexpression (p=0.05). Benefit of bevacizumab was present only in the subgroup of patients with PFI &lt; 12 months (mPFS 18.6 versus 10.4 months, p=0.002) and in the subgroup of patients with cyclin E1 overexpression (mPFS 16.3 versus 7.0 months, p=0.010).
Conclusions:Markers of resistance to chemotherapy such as cyclin E1 overexpression and PFI identify patients with the greatest benefit of bevacizumab. This data could help to discern between maintenance treatment options in the era of PARP inhibitors and anti-angiogenics.
Citation Format: Adriana Regina G. Ribeiro, Marcella M. Salvadori, Louise de Brot, Graziele Bovolim, Henrique Mantoan, Felipe Ilelis, Mariana R. Alves, Nayra Soares Amaral, Solange M. Sanches, Joyce Lisboa, Elizabeth S. dos Santos, Ronaldo Pereira, Fabricio S. Castro, Joao Paulo S. Lima, Andrea P. Guimaraes, Glauco Baiocchi, Alexandre Andre B. Da Costa. Cyclin E1 overexpression identifies patients with greater benefit from bevacizumab in platinum sensitive recurrent ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3157.