Andrew Clamp MD, PhD, ESMO Berlin: Weekly Dose-Dose Chemotherapy Brings Big Survival Benefit for Patients with High-Risk Ovarian Cancer

An interview with: Andrew Clamp MD, PhD, Consultant Medical Oncologist, Christie Hospital, Manchester, UK BERLIN, Germany—An important therapeutic gain in terms of overall- and progression-free survival has been achieved merely by changing the chemotherapy dose schedule given to patients with high-risk stage three or four epithelial ovarian cancer. This was reported from the ICON8B: GCIG phase-three randomised trial by Andrew Clamp MD PhD of the Christie Hospital in Manchester, England, at the 2025 Annual Congress of the European Society for Medical Oncology. Dr. Clamp discussed the findings with our reporter, Peter Goodwin. Audio Journal of Oncology interview: Andrew Clamp MD, PhD IN: “[GOODWIN] I’m at the European ….. OUT: ….Journal of Oncology, I’m Peter Goodwin”  7:21secs https://www.annalsofoncology.org/article/S0923-7534(25)02624-9/pdf ESMO ABSTRACT: 1064O – ICON8B: GCIG phase III randomised trial comparing first-line weekly dose-dense chemotherapy + bevacizumab to three-weekly chemotherapy + bevacizumab in high-risk stage III-IV epithelial ovarian cancer (EOC): Final overall survival (OS) analysis Speaker: Andrew R. Clamp (Manchester, United Kingdom) Authors: Andrew R. Clamp (Manchester, United Kingdom) Iain McNeish (London, United Kingdom) Domenico Radice (London, United Kingdom) Rosemary Lord (Liverpool, United Kingdom) Agnieszka Michael (Guildford, United Kingdom, Surrey) Audrey Cook (Cheltenham, United Kingdom) Roshan Agarwal (Northampton, United Kingdom, Northamptonshire) Axel Walther (Bristol, United Kingdom) Sarah P. Blagden (Oxford, United Kingdom) Dearbhaile O’Donnell (Dublin, Ireland) James D. Brenton (Cambridge, United Kingdom) Sudha Sundar (Birmingham, United Kingdom) Cristiana Sessa (Bellinzona, Switzerland) Laura R. Murphy (London, United Kingdom) Francesca Schiavone (London, United Kingdom) Aleksandra Gentry-Maharaj (London, United Kingdom) Richard S. Kaplan (London, United Kingdom) Mahesh K. Parmar (London, United Kingdom, London) Jonathan A. Ledermann (London, United Kingdom) ESMO Abstract Background In ICON8B the use of dose-dense weekly paclitaxel (ddwT) with 3-weekly (q3w) carboplatin (C) and bevacizumab (BEV) as first-line treatment improved median progression-free survival (PFS) by 5.5 months (m) compared to standard q3w paclitaxel (T) dosing with C+BEV (22.2m vs 16.7m; Hazard Ratio (HR) 0.75, 95% CI 0.62-0.90 p=0.002). We now report the final OS analysis conducted at trial closure. Methods Eligible participants (pts) with high-risk stage III (residual disease >1cm diameter after immediate primary surgery (IPS) or requirement for primary chemotherapy) or stage IV EOC 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 PFS improvement with q3wCddwT vs q3wCT. OS was a key secondary outcome and pts were followed for survival endpoints until trial closure on 18th Dec 2024 at end of academic funding. Results From 07/2015 to 03/2020 579 pts were randomised to arms B1 + B3. Median age was 64 years; 91% had High Grade Serous Carcinoma; 93% Stage IIIc/IV; 84% primary chemotherapy with planned delayed primary surgery, 14% IPS, 2% inoperable; 50.2% cases sequenced for germline BRCA1/2 mutations. After a median follow-up of 72.0m, 411 deaths were reported (197 in B3; 214 in B1). Median OS was 49.8m (95% CI 43·7-54.5m) in B3 and 39.6m (95% CI 34·7-45·0m) in B1 (HR 0·79, 95% CI 0·65-0·95, p=0·010). In pts receiving primary chemotherapy, median OS was 47.3m (95% CI 42.0-52.6m) in B3 and 37.1m (95% CI 32.3-42.1m) in B1. Conclusions In pts with high-risk stage III-IV EOC, the use of ddwT in combination with q3w C + BEV as first-line systemic therapy improves median OS by 10.2m compared to q3w T dosing. ddwT with q3wC+BEV should now be considered a standard-of-care first-line treatment option in this group. Further research is required to determine whether efficacy of this regimen is impacted by tumour homologous recombination deficiency and intrinsic chemosensitivity. Clinical trial identification ISRCTN10356387. Legal entity responsible for the study University College London. Funding Cancer Research UK and Medical Research Council.

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