Article Text
Abstract
Introduction/Background Antiangiogenic therapy using bevacizumab has proven effective for patients with advanced ovarian cancer. However, there is still an unmet need in ovarian cancer to identify patients who benefit from such treatment. The nine-protein signature score vascular endothelial growth factor inhibition response predictor (ViRP) has been shown predictive for response in patients with HER2-negative breast cancer.
Methodology ICON7 was an international, phase 3, open-label, randomized trial assigning patients with either high-risk early-stage disease or more advanced disease to standard chemotherapy +/- bevacizumab, given concurrently and continued in maintenance therapy. DASL gene expression arrays have been performed on FFPE tissue from patients enrolled in the German contribution to the trial. The mRNA based ViRP score was calculated using quantile normalized and probe averaged mRNA expression values and its association with clinical outcome was studied.
Results mRNA expression was available for 359 patients, of whom 189 patients were treated with bevacizumab. We used the earlier determined cut-off <0.3 as a positive ViRP score. Clinical characteristics were balanced across the groups with positive/negative ViRP score. Patients with a positive ViRP score have statistically significant longer progression-free survival with a median of 26.7 months compared to 19.1 months in patients with negative ViRP score (HR 0.58, 95%CI 0.41–0.84, p=0.003). Furthermore, overall survival was significantly longer in patients with a positive ViRP score with median OS not reached compared to 48.2 months in patients with negative ViRP score (HR 0.63, 95%CI 0.41–0.97, p=0.033). Among patients treated with chemotherapy alone ViRP was significantly associated with PFS (HR 0.67, 95%CI 0.46–0.97, p=0.034), but not OS (HR 0.80, 95%CI 0.52–1.23, p=0.31).
Conclusion The ViRP score is predictive for survival benefit of treatment with chemotherapy with bevacizumab in patients with ovarian cancer. This indicates a tumor agnostic signal which identifies patients deriving the largest benefit from adding bevacizumab.
Disclosures KL: Receipt of grants/research supports: GSK, research funding paid to
Institution; Receipt of honoraria or consultation fees: Advisory board fees: Astra Zeneca, Nycode, GSK, Eisai
FH: Receipt of honoraria or consultation fees: Novocure, PharmaMar, Astra Zeneca, Roche, Tesaro, GSK, Clovis, Amedes, NewOncology, Zailab
RK: Receipt of honoraria or consultation fees: Astra Zeneca, MSD; GSK, Roche, Novocure
JS: Research Funding: Institution: AZ, Clovis Oncology, Merck, Bayer, PharmaMar, Pfizer, Tesaro, MSD Oncology, Roche. Consulting/Ad Bds: AZ, Clovis Oncology, PharmaMar, Merck, Pfizer, Tesaro, MSD Oncology, Lilly, Novocure, J&J, Roche, Ingress Health, Riemser, Sobi, GSK, Novartis; Honoraria: AZ, Eisai, Clovis Oncology, Olympus Medical Systems, J&J, PharmaMar, Pfizer, Teva, Tesaro, MSD Oncology, GSK, Bayer; Travel, Accommodations, Expenses: AZ, Clovis Oncology, PharmaMar, Roche Pharma AG, Tesaro, MSD Oncology, Olympus.