An International Phase III Randomised Trial of Dose Fractionated Chemotherapy Compared to Standard Three Weekly Chemotherapy, Following Immediate Primary Surgery or as Part of Delayed Primary Surgery, for Women With Newly Diagnosed Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer (ICON8)

Newly diagnosed stage IC-IV epithelial ovarian cancer

1566 (20% stage IC-II, 60% stage III, 20% stage IV)

First-line

Open-Label, Randomized

PFS, OS, evaluated per RECIST

Standard of Care (SoC): CarboPt AUC5 or AUC6+Pac 175mg/m2 every 3 weeks
CarboPt q3w+Pac qw: CarboPt AUC5 or AUC6 every 3 weeks+Pac 80mg/m2 weekly
CarboPt+Pac qw: CarboPt AUC2+Pac 80mg/m2 weekly

SoC (n=522) vs CarboPt q3w+Pac qw (n=523) vs CarboPt+Pac qw (n=521):

PFS: 25 vs 25.8 vs 25.9 months
OS: 47.4 vs 54.8 vs 53.4 months, HR: 0.87 (0.73-1.05); HR: 0.91 (0.76-1.09)

Exploratory analysis, patients planned for neoadjuvant chemotherapy followed by IDS w/ RECIST and/or GCIG CA125-evaluable disease:
RECIST (n=564): ORR: 62%; PFS: 14.4 (CR or PR) vs 13.3 months (SD); R0 obtained: 56 (CR or PR) vs 42% (SD)
GCIG-CA125 (n=727): ORR: 84%; PFS: 13.8 (w/ CA125 response) vs 9.7 months (w/o CA125 response); R0 obtained: 50 (w/ CA125 response) vs 30% (w/o CA125 response)

SoC vs CarboPt q3w+Pac qw vs CarboPt+Pac qw:
Serious AE:
Grade 3-4 AE: anemia (6 vs 12 vs 5%), decreased neutrophil counts (14 vs 35 vs 30%), decreased white blood cells (5 vs 16 vs 14%)

Weekly dose-dense chemotherapy can be delivered successfully as first-line treatment for epithelial ovarian cancer but does not significantly improve PFS compared with standard chemotherapy every 3 weeks

Clamp AR et al. Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treatment (ICON8): primary progression free survival analysis results from a GCIG phase 3 randomised controlled trial. Lancet (2019) 394(10214):2084-2095
https://www.ncbi.nlm.nih.gov/pubmed/31791688

Morgan RD et al. Objective responses to first-line neoadjuvant carboplatin-paclitaxel regimens for ovarian, fallopian tube, or primary peritoneal carcinoma (ICON8): post-hoc exploratory analysis of a randomised, phase 3 trial. Lancet Oncol (2021) 22(2):277-288
https://pubmed.ncbi.nlm.nih.gov/33357510/

Clamp AR et al. Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal cancer treatment (ICON8): overall survival results from an open-label, randomised, controlled, phase 3 trial. Lancet (2022) 23(7):919-930
https://pubmed.ncbi.nlm.nih.gov/35690073/