Response to neoadjuvant chemotherapy in ICON8: A GCIG phase III randomised trial evaluating weekly dose-dense chemotherapy integration in first-line epithelial ovarian/ fallopian tube/ primary peritoneal carcinoma (EOC) treatment

Background: Neoadjuvant carboplatin-paclitaxel (CT) with delayed primary surgery (DPS) after 3 cycles is a standard-of-care option for women with bulky FIGO stage IIIc-IV EOC. However, radiological and biochemical response to neoadjuvant CT has not been prospectively evaluated nor compared with DPS outcome and progression-free survival (PFS). Methods: ICON8 is a phase III randomised trial that compared standard 3-weekly CT with 2 dose-dense weekly CT regimens. Patients could enter after primary surgery or receive neoadjuvant treatment with planned DPS. Radiological response to neoadjuvant CT was evaluated using RECIST v1.1. Serum CA125 was measured 3-weekly per protocol and evaluated using GCIG criteria. Results: 779 patients entered ICON8 with planned DPS after neoadjuvant CT. DPS was performed in 602 (536 after 3-4 cycles; 65 after 5/6 cycles; data missing 1). RECIST and CA125 response data were available for 531 and 726 respectively. No differences in response were noted between trial arms, so a combined analysis was performed. Best RECIST response (RR) pre-DPS was 61% (CR 4%, PR 57%, SD 33%, PD 6%). Median pre-operative change in marker lesions was -14.5% in patients with SD. GCIG CA125 response rate was 84%, including 71% (123/173) in patients with RECIST SD. Comparison of surgical feasibility, cytoreductive outcomes and PFS with ORR are presented in the table.Table: 943PDDPS Outcome by RECIST GroupPD N = 32SD N = 177PR/CR N = 322Total N = 531Surgery not performed8 (31%)28 (17%)28 (9%)64 (13%)Inoperable03 (2%)5 (2%)8 (2%)Debulked to no visible residual disease14 (54%)69 (42%)166 (54%)249 (50%)Debulked to ≤ 1cm residual disease2 (8%)41 (25%)74 (25%)117 (23%)Debulked to > 1cm residual disease2 (8%)24 (15%)34 (11%)60 (12%)Surgical outcome missing6121533Median PFS (months)5.014.716.4 Open table in a new tab Conclusions: RR to neoadjuvant CT in ICON8 was 61% and was not improved by dose-dense CT. PD is rare following neoadjuvant CT and SD by RECIST incorporates many women with definite reduction in disease burden. GCIG CA125 criteria overestimate response compared to RECIST. Both PFS and complete/optimal debulking rates were similar in SD and CR/PR groups, reinforcing that patients with SD should be offered DPS. Clinical trial identification: ISRCTN: ISRCTN10356387; EudraCT: 2010-02209-16. Legal entity responsible for the study: University College London. Funding: Cancer Research UK. Disclosure: A.R. Clamp: Research grants, travel expenses and advisory board: AstraZenenca, I.A. McNeish: Advisory boards: AstraZeneca, Clovis Oncology, Tesaro, Takeda. All other authors have declared no conflicts of interest.