Introduction/Background First-line phase III trials in stage III/IV Epithelial Ovarian Cancer (EOC) have shown improved survival both with addition of bevacizumab (BEV) to three-weekly (q3w) carboplatin (C)-paclitaxel (T) and integration of weekly dose-dense paclitaxel (ddwT) with carboplatin compared to q3wCT alone. ICON8B, a 3-arm trial, compared BEV+q3wCT versus (vs) BEV+q3wCddwT vs q3wCddwT in high-risk stage III (residual disease >1cm diameter after primary surgery or requirement for primary chemotherapy) and stage IV EOC.
Methodology Eligible patients were randomised 1:1:1 to Arm B1 (standard- q3w C AUC5/6+q3w T 175mg/m2+ q3w BEV 7.5mg/kg); Arm B2- q3w C AUC5/6+ddwT 80mg/m2; Arm B3- q3w C AUC5/6+ddwT 80mg/m2+ q3w BEV 7.5mg/kg. Up to six cycles chemotherapy and 18 BEV cycles were administered. Arm B2 recruitment discontinued after ICON8 saw no evidence of progression-free survival (PFS) improvement with q3wCddwT vs q3wCT. The consolidated Arm B1 vs B3 trial targeted 509 PFS events to detect B3vB1 HR=0.75 with 90% power.
Results 707 patients randomised from 07/2015 – 03/2020 (B1=292, B2=129, B3=286), median age 64 years, 94% ECOG Performance Status 0-1, 53% stage IIIC, 40% stage IV, 91% High Grade Serous histology. 14% upfront surgery, 84% planned Delayed Primary Surgery, 2% no surgery planned. 88%:83%:82% completed 6 cycles carboplatin-based chemotherapy and 45%:51%:58% experienced ≥grade 3 toxicities in B1:B2:B3. 49%:61% completed 18 cycles bevacizumab in B1:B3. Median 59.0 months follow-up (07/2023-B1 and B3). Given slow additional event rate, the study committee concluded 465 progression events were sufficient for primary analysis, giving 87% power for the targeted effect size of 0.75. PFS was better in B3 compared to B1. Median PFS 16.7 months B1 vs 22.2 months B3 (HR=0.75, 95% CI=0.62-0.90, p=0.002). Median OS; 40.9 months B1 vs 51.1 months B3 (HR=0.77, 95% CI=0.62-0.96, p=0.020).
Conclusion In primary treatment of high-risk stage IIIC/IV EOC, BEV+q3wCddwT improves median PFS by 5.5 months compared to BEV+q3wCT.
Disclosures Andrew Clamp- Receipt of grants/research support- institutional funding from AZ, Merck, Advenchen, Eisai, Verastem, Novartis. Receipt of honoraria or consultation fees- GSK, Clovis, Immunogen, MSD. Participation in a company sponsored speakers bureau-GSK.
Iain McNeish- Receipt of grants/research support- institutional funding from AZ, Receipt of honoraria or consultation fees- AZ, GSK, Clovis Oncology, Roche, OncoC4, ScanCell, Theolytics
Rosemary Lord- Receipt of honoraria or consultation fees-GSK.
Marcia Hall-Receipt of grants/research supports: BMS, Clovis Oncology, Merck. Receipt of honoraria or consultation fees: Clovis Oncology, Immunogen
Sharadah Essapen- Nil
Audrey Cook- Nil
Axel Walther-Receipt of honoraria or consultation fees: Clovis, GSK.
Sarah Blagden-Receipt of grants/research supports: Institutional funding for clinical research-Nucana plc, Astex, Nurix, Tesaro, Redx, MSD, UCB, Regeneron, Biontech. Receipt of honoraria or consultation fees: Oxford Drug Design, Simbec-Orion, Ellipses, Theolytics. Other support: Founder and director of RNA Guardian Ltd.
Dearbhaile O’Donnell- Nil
James Brenton- Receipt of grants/research support: GE Healthcare, Varsity Pharmaceuticals. Receipt of honoraria or consultation fees: Clovis Oncology, GSK, AstraZeneca, Stock shareholder: Tailor Bio
Sudha Sundar- Receipt of honoraria or consultation fees: AstraZeneca, GSK, MSD. Participation in a company-sponsored speakers bureau: Astra Zeneca, MSD
Adrian Cook- Nil
Domenico Radice- Stock ownership: GSK
Francesca Schiavone- Nil
Aleksandra Gentry-Maharaj-Receipt of grants/research supports: ILOF, RNA Guardian, Micronoma, Mercy Bioanalytics
Richard Kaplan- Nil
Mahesh Parmar- Nil
Jonathan Ledermann-Receipt of grants/research supports: AstraZeneca; MSD Receipt of honoraria or consultation fees:
AstraZeneca, Artios Pharma, Eisai, Bristol Myers Squibb, VBL Therapeutics, Nuvation, Ellipses, Immagen, Merck/MSD Participation in a company sponsored speaker’s bureau: AstraZeneca; GlaxoSmith Kline; Neopharm; Clovis Oncology
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