The relative benefit of bevacizumab in ovarian cancer (OC) patients is greater the more the disease becomes platinum-resistant. Among other mechanisms of action, antiangiogenic agents may induce homologous recombination deficiency. Cyclin E1 (CCNE1) overexpression is a proposed marker of platinum resistance and is mutually exclusive with deficiency in homologous recombination. In this study, we evaluated the predictive value of CCNE1 expression with regard to the efficacy of bevacizumab. We retrospectively evaluated data from patients with platinum-sensitive recurrent OC who were treated with chemotherapy (CT) plus bevacizumab (Bev group) or CT alone (CT group) at a tertiary cancer centre from 2005 to 2017. The two groups were paired according to histology, platinum-free interval (PFI) and number of previous treatment lines. Progression-free survival (PFS) was compared between groups by log rank test and Cox regression. A total of 124 patients were included, with 62 in each group. The groups were well balanced regarding histology, PFI and number of previous treatment lines. Median PFS (mPFS) was 19.5 months for the Bev group versus 16.0 months for CT group (p = 0.150). By multivariate analysis, the HR for PFS was 2.25 (95% CI: 1.10-4.60) for CCNE1 overexpression. The benefit of bevacizumab was larger in the subgroups of patients with PFI 6-12 months (mPFS 18.6 versus 10.4 months, p = 0.002) and CCNE1 overexpression (mPFS 16.3 versus 7.0 months, p = 0.010). In conclusion, CCNE1 overexpression and PFI may suggest which patients will receive the greatest benefit from bevacizumab. These data, if confirmed by other studies, could help better select patients for antiangiogenic therapy.

No abstract

No 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 > 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 > 12 months showed a mPFS of 20.0 months vs. 15.5 for patients with a PFI < 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 < 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.