Final OS results from the ENGOT-ov13/GTG-UK/ICON8B trial

Dr Andrew Clamp, consultant medical oncologist at The Christie NHS Foundation Trust in Manchester and Chief Investigator of the ENGOT-ov13/GTG-UK/ICON8B study summarized the final OS results of the phase III, ICON8B trial that investigated the integration of concurrent and maintenance bevacizumab with weekly dose-dense paclitaxel in the first-line management of patients with high-risk stage III and IV epithelial ovarian cancer.

Initially, ICON8B comprised three treatment arms: arm B1 with three-weekly carboplatin–paclitaxel plus concurrent and maintenance bevacizumab; arm B2 with dose-dense weekly paclitaxel and carboplatin without bevacizumab; and arm B3 combining both dose-dense paclitaxel and bevacizumab. Two years after trial initiation, the chemotherapy-only arm (B2) was closed following the ICON8 trial results, which showed no significant improvement in PFS with weekly paclitaxel compared to standard three-weekly chemotherapy. Recruitment to the remaining two bevacizumab-containing arms continued until March 2020.

At the 2023 ESGO congress, we reported a significant improvement in median PFS with the combined regimen (arm B3) compared to bevacizumab with standard chemotherapy (arm B1). The final OS analysis, conducted at the end of 2024, confirmed a statistically and clinically meaningful survival advantage. Median OS increased from 39.6 months in arm B1 to 49.8 months in arm B3, representing a 10.2-month improvement. Exploratory subgroup analysis indicated that the greatest benefit occurred among patients who had received neoadjuvant chemotherapy followed by delayed cytoreductive surgery, a group that constituted the majority of the trial population.

These findings establish the combination of bevacizumab with dose-dense weekly paclitaxel and carboplatin as an effective first-line treatment option for patients with high-risk stage III–IV ovarian cancer, particularly those managed with neoadjuvant therapy. A limitation of the study is that it was conducted before the widespread introduction of PARP inhibitors into first-line maintenance therapy. Comprehensive data on BRCA mutation and HRD status are not yet available for all participants. Nonetheless, ICON8B supports this regimen as a standard-of-care option, with the potential for subsequent integration of PARP inhibitors, such as olaparib, for patients with HRD-positive disease following completion of chemotherapy.