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#159 ICON8B: GCIG phase III randomised trial comparing weekly dose-dense chemotherapy + bevacizumab to three-weekly chemotherapy+ bevacizumab in first-line high-risk stage III-IV epithelial ovarian cancer treatment: primary progression-free survival analysis
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  1. Andrew Clamp1,2,
  2. Iain Mcneish3,
  3. Rosemary Lord4,
  4. Marcia Hall5,
  5. Sharadah Essapen6,
  6. Audrey Cook7,
  7. Roshan Agarwal8,
  8. Axel Walther9,
  9. Sarah Blagden10,
  10. Dearbhaile O’Donnell11,
  11. James D Brenton12,13,
  12. Sudha Sundar14,
  13. Cristiana Sessa15,
  14. Adrian Cook16,
  15. Domenico Radice16,
  16. Francesca Schiavone16,
  17. Aleksandra Gentry-Maharaj16,
  18. Richard Kaplan16,
  19. Mahesh Kb Parmar16 and
  20. Jonathan Ledermann17
  1. 1The Christie NHS Foundation Trust, Manchester, UK
  2. 2University of Manchester, Manchester, UK
  3. 3Imperial College London, London, UK
  4. 4The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK
  5. 5Mount Vernon Cancer Centre, Northwood, UK
  6. 6Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK
  7. 7Gloucestershire Oncology Centre, Cheltenham, UK
  8. 8University Hospitals of Northamptonshire, Northampton, UK
  9. 9Bristol Cancer Institute, Bristol, UK
  10. 10University of Oxford, Oxford, UK
  11. 11Cancer Trials Ireland, Dublin, Ireland
  12. 12University of Cambridge, Cambridge, UK
  13. 13Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
  14. 14University of Birmingham, Birmingham, UK
  15. 15Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
  16. 16Medical Research Council Clinical Trials Unit at University College London, London, UK
  17. 17University College London Cancer Institute, London, UK

Abstract

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

Roshan Agarwal-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

Cristiana Sessa-Nil

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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