761P - Anti-angiogenic therapy in first-line treatment of low-grade serous ovarian cancer: Exploratory meta-analysis of the prospective AGO-OVAR 11/12/16 studies

Background

Low-grade serous ovarian cancer (LGSOC), a subtype accounting for 5–10% of all epithelial ovarian cancers, exhibits significantly reduced sensitivity to chemotherapy in contrast to high-grade serous ovarian cancer (HGSOC). Retrospective studies have investigated the efficacy of anti-angiogenic therapy (AAT) in LGSOC, revealing promising outcomes but prospective evidence is rare. Our analysis investigates the efficacy of AAT in patients (pts) with LGSOC across three prospective randomised phase III trials, both in individual and pooled analyses.

Methods

LGSOC pts of AGO-OVAR 11 (Carboplatin/Paclitaxel [C/P] +/- Bevacizumab [Bev]), AGO-OVAR 12 (C/P + Nintedanib/Placebo [Pla]) and AGO-OVAR 16 (Pazopanib/Pla maintenance following C/P) were included in this analysis. Effect of AAT was analysed by Kaplan-Meier method and log-rank tests regarding progression-free survival (PFS). P values presented were two-tailed, and p<0.05 was considered as statistically significant.

Results

A total of 137 LGSOC pts were analysed: OVAR 11 (19 pts), OVAR 12 (72 pts), and OVAR 16 (46 pts). LGSOC pts had less residual tumor after surgery (p=0.002), less presence of ascites (p<0.001), and less extend of peritoneal carcinomatosis (p<0.001) compared to HGSOC. In the individual analyses of each study as well as in the pooled analysis, we could not show a statistical significant benefit in terms of PFS with AAT: OVAR 11 (Hazard Ratio [HR] 0.87 [CI 0.15-5.23], p=0.88), OVAR 12 (HR 0.80 [CI 0.41-1.57], p=0.52), OVAR 16 (HR 0.60 [CI 0.24-1.46], p=0.25) and OVAR 11/12/16 (HR 0.78 [CI 0.47-1.29], p=0.33). This was independent of residual tumor, ascites, and peritoneal carcinomatosis.

Conclusions

Our study could not show a significant impact of AAT in the first-line treatment of LGSOC patients with a high rate of complete resection. Further analyses in large datasets are indicated to identify the subgroup responsible for the marginal positive impact observed in our analysis.

Clinical trial identification

OVAR 11: ISRCTN91273375, OVAR12: NCT01015118, OVAR16: NCT00866697.

Editorial acknowledgement

Legal entity responsible for the study

AGO Study Group.

Funding

Has not received any funding.

Disclosure

B. Czogalla: Financial Interests, Personal, Invited Speaker: AstraZeneca. F. Trillsch: Financial Interests, Personal, Invited Speaker: AstraZeneca, ImmunoGen, AstraZeneca, MSD, Tesaro/GSK; Financial Interests, Personal, Advisory Board: Eisai, ImmunoGen, MSD, Tesaro/GSK; Financial Interests, Personal and Institutional, Research Grant: SAGA diagnostics; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Steering Committee Member: AstraZeneca; Financial Interests, Institutional, Coordinating PI: ImmunoGen. F. Heitz: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, GSK, NovoCure; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK. S. Mahner: Financial Interests, Personal, Advisory Board, Honoraria & reimbursement: AbbVie, AstraZeneca, Clovis, Eisai, Novartis, Olympus, Seagen; Financial Interests, Personal, Invited Speaker, Honoraria & reimbursement: GSK, MSD, Pfizer, Roche, Tesaro, Hubro, Nykode; Financial Interests, Institutional, Research Grant: AstraZeneca, Eisai, GSK, MSD, Roche, Tesaro. N. de Gregorio: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Myriad, Novartis, MSD, GSK, Clovis, Gilead; Other, travel expenses: AstraZeneca, Gilead. F. Selle: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK Tesaro, MSD, AbbVie; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK Tesaro, MSD, Eisai, Seagen. P. Wimberger: Financial Interests, Research Funding: Amgen, AstraZeneca, MSD, GSK, Novartis, Pfizer, Roche Pharma, Clovis, Lilly; Financial Interests, Other: Amgen, AstraZeneca, MSD, GSK, Novartis, Pfizer, Roche Pharma, Clovis, Teva, Eisai, Lilly, Gilead, Daichii Sankyo; Financial Interests, Advisory Board: Amgen, AstraZeneca, MSD, GSK, Novartis, Pfizer, Roche Pharma, Clovis, TEVA, Eisai, Lilly, Gilead, Daichii Sankyo. M.R. Mirza: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, Karyopharm, Merck, Zailab, BioNTech, Daiichi Sankyo, Eisai, ImmunoGen/AbbVie, Incyte, Regeneron; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK; Financial Interests, Personal, Member of Board of Directors: Karyopharm; Financial Interests, Personal, Stocks/Shares: Karyopharm; Financial Interests, Institutional, Research Grant: GSK, AstraZeneca, ultimovacs, Apexigen; Financial Interests, Institutional, Trial Chair: Deciphera; Non-Financial Interests, Advisory Role: Ultimovacs; Non-Financial Interests, Member, Member of Prix Galien Awards Committee: Prix Galien Foundation. J. Sehouli: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, MSD, Tesaro, ImmunoGen, Tubulis, Novocure, Incyte; Financial Interests, Personal, Invited Speaker: Eisei; Financial Interests, Institutional, Funding: Roche, GSK, AstraZeneca; Financial Interests, Institutional, Coordinating PI: Novocure; Non-Financial Interests, Institutional, Proprietary Information: ENGOT/NOGGO; Non-Financial Interests, Leadership Role, Council Member: ESGO; Non-Financial Interests, Leadership Role: North-Eastern German Society of Gynecological Oncology (NOGGO), Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO), Pab-Arabian Research Society of Gynecological Oncology (PARSGO). F. Hilpert: Financial Interests, Personal, Advisory Board: MSD, ImmunoGen; Financial Interests, Personal, Invited Speaker: MSD, GSK, AstraZeneca, Novartis. L.C. Hanker: Financial Interests, Personal, Advisory Board: Amgen, Roche, GSK, MSD, AstraZeneca, Eisai, Novartis, ImmunoGen. J. Pfisterer: Financial Interests, Personal, Advisory Board: Roche, Amgen, AstraZeneca, GSK; Financial Interests, Institutional, Coordinating PI: Roche, GSK. P. Harter: Financial Interests, Personal, Advisory Board, Value includes honoraria for lectures: AstraZeneca; Financial Interests, Personal, Advisory Board, includes honoraria for lectures: GSK, Roche, MSD; Financial Interests, Personal, Invited Speaker: Amgen, Stryker, Zailab, Eisai, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Clovis, ImmunoGen, Novartis, Mersana, Miltenyi, Exscientia; Financial Interests, Personal, Other, IDMC member: Sotio; Financial Interests, Institutional, Trial Chair: AstraZeneca, Roche, GSK, ImmunoGen; Financial Interests, Institutional, Local PI: Genmab; Financial Interests, Institutional, Funding: Seagen, Clovis; Financial Interests, Institutional, Other, Co-investigator: Novartis; Non-Financial Interests, Principal Investigator: AstraZeneca; Other, Travel support for conference: AstraZeneca. A. du Bois: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK / Tesaro; Financial Interests, Personal, Invited Speaker: Zodiac. All other authors have declared no conflicts of interest.