ICON8B OS data support a new SoC for epithelial ovarian cancer

In the final overall survival (OS) analysis of the phase III ICON8B trial, first-line treatment with bevacizumab in combination with a chemotherapeutic regimen comprising carboplatin Q3W and dose-dense paclitaxel QW improved survival in women with high-risk stage III-IV epithelial ovarian cancer.

ICON8B enrolled 707 women (median age at randomization 64 years) with newly diagnosed high-risk stage III (residual disease >1 cm diameter after immediate primary surgery [IPS] or requirement for primary chemo) or stage IV epithelial ovarian cancer. They were randomized 1:1:1 to carboplatin AUC5 Q3W + paclitaxel 175 mg/m² Q3W + bevacizumab 7.5 mg/kg Q3W (arm B1), carboplatin AUC5 Q3W + paclitaxel 80 mg/m² QW (arm B2), or carboplatin AUC 5 Q3W + paclitaxel 80 mg/m² QW + bevacizumab 7.5 mg/kg Q3W (arm B3). Recruitment for arm B2 was discontinued in 2017 due to the negative progression-free survival (PFS) results. Up to six chemo cycles and 18 bevacizumab cycles were administered.

Ninety-one percent of the participants had high-grade serous histology, 93 percent had FIGO stage IIIC/IV disease, 85 percent had planned delayed primary surgery (DPS), and 14 percent had IPS. Five percent of patients had a documented germline BRCA pathogenic variant, and 41 percent had germline BRCA wild-type.

OS, updated PFS

After a median follow-up of 72 months, the B3 regimen prolonged OS by 10.2 months as opposed to the B1 regimen (median 49.8 vs 39.6 months; hazard ratio [HR], 0.79, 95 percent CI, 0.65–0.95; p=0.010). [ESMO 2025, abstract 1064O]

When stratifying by timing of surgery, the results still favoured the B3 over the B1 regimen in the DPS subgroup (median OS 47.3 vs 37.1 months; HR, 0.78, 95 percent CI, 0.64–0.96; p=0.015). The effect was less pronounced in the IPS subgroup (median OS 64.4 vs 62.7 months; HR, 0.81, 95 percent CI, 0.43–1.54; p=0.36).

There were no statistically significant interactions observed between treatment effect, disease stage, histological subtype, and germline BRCA status on subgroup analysis, but there was a trend toward an OS benefit among participants who had non-high-grade serous histology (HR, 0.47, 95 percent CI, 0.24–0.95).

The B3 regimen also increased the median PFS by 4.9 months in the updated PFS analysis (21.4 vs 16.5 months; HR, 0.72, 95 percent CI, 0.60–0.86; p=0.0003).

Key safety findings

“The safety profile was as expected from prior clinical experience,” said Dr Andrew Clamp from The Christie National Health Service Foundation Trust, Manchester, UK, during his presentation at ESMO 2025.

Compared with the B1 arm, the B3 arm had a higher incidence of grade ≥2 anaemia. The rates of peripheral sensory neuropathy were similar across treatment arms, as were those of venous thromboembolic events. There were more hypertension events in the B1 vs the B3 arm.

“There was a small increase in the incidence of low-grade wound complications or dehiscences in patients who received bevacizumab, predominantly among those who went through a neoadjuvant pathway, but this did not prevent patients from proceeding to maintenance therapy,” Clamp said.

Potentially practice-changing

“For nearly 30 years, the platinum-paclitaxel chemo doublet administered on a once-every-3-week schedule has been the cornerstone of first-line multimodality management of epithelial ovarian cancer,” said Clamp. “It is either given postoperatively after primary cytoreductive surgery or increasingly frequently as primary neoadjuvant treatment with a plan for delayed surgical cytoreduction.”

Studies have shown two strategies that could improve OS in high-risk stage III or IV disease: by adding concurrent and maintenance bevacizumab and by incorporating dose-dense paclitaxel QW. [Lancet Oncol 2015;10:928-936; Lancet Oncol 2013;14:1020-1026]

The current findings support the primary PFS analysis showing a significantly longer PFS with the B3 vs the B1 regimen (median 22.2 vs 16.7 months; HR, 0.75, 95 percent CI, 0.62–0.90; p=0.002). [Int J Gynecol Cancer 2023;33:A424]

“We therefore conclude that bevacizumab in combination with carboplatin Q3W and dose-dense paclitaxel QW should be considered a standard-of-care option in the first-line management of these patients,” said Clamp.

“[The OS] improvement is clinically meaningful. Paclitaxel QW also has advantages such as less alopecia, and it will be interesting to compare quality of life outcomes between the two regimens,” commented Professor Isabelle Ray-Coquard from Centre Léon Bérard, Lyon, France, in a press release.

Ray-Coquard cited certain limitations, such as the lack of BRCA mutation stratification. She also noted that the study did not reflect current standards of care, such as the use of poly (ADP-ribose) polymerase (PARP) inhibitors in patients with homologous recombination deficiency (HRD) tumours or hyperthermic intraperitoneal chemo during debulking surgery, which are associated with improved survival outcomes.

“We need to be clear about whether PARP inhibitor tolerance will be affected by dose-dense therapy. Real-world data could be helpful,” said discussant Dr David Tan from the National University Cancer Institute, Singapore, at ESMO 2025.

Clamp noted that translational work is underway to ascertain the interaction between intrinsic tumour chemosensitivity and HRD and the efficacy of dose-dense treatment.