Mature survival data from the phase 3 ICON8 trial revealed no significant difference between administering weekly dose-dense chemotherapy and standard 3-weekly chemotherapy as front-line therapy for patients with epithelial ovarian cancer.
First-line weekly dose-dense chemotherapy did not improve overall survival (OS) or progression-free survival (PFS) when compared with standard 3-weekly chemotherapy in women epithelial ovarian cancer, according to findings from the phase 3 ICON8 trial (NCT01654146).1
Findings reported in the Lancet Oncology examining a cohort of patients, predominantly made up of European women with epithelial ovarian cancer, demonstrated that first-line weekly dose-dense chemotherapy should not be used as part of standard multimodality front-line therapy in this patient group.
The open-label, randomized, controlled, phase 3 trial ICON8 trial enrolled women aged 18 years or older with newly diagnosed stage IC-IV epithelial ovarian, primary peritoneal, or fallopian tube carcinoma. In order to be eligible in the trial, patients were also required to have an ECOG performance status of 0-2, a life expectancy greater than 12 weeks, and adequate bone marrow function, liver function, and renal function.
Those enrolled were recruited across 117 hospitals in the UK, Australia and New Zealand, Mexico, South Korea, and Ireland. Those enrolled were able to enter the trial after immediate primary surgery or with planned delayed primary surgery during chemotherapy. Patients also were able to have no planned surgery.
Patients were randomized in a 1:1:1 ratio to either the control group/ group 1 which consisted of 3-weekly carboplatin area under the curve (AUC) 5 or AUC6 and 3-weekly paclitaxel 175 mg/m2, group two who were given 3-weekly carboplatin AUC5 or AUC6 and weekly paclitaxel 80 mg/m2, or group 3 who were administered weekly carboplatin AUC2 and weekly paclitaxel 80 mg/m2. All of these doses were administered through intravenous infusion for a total of 6 21-day cycles.
The coprimary end points of the trial consisted of PFS and OS, with comparisons done between group 2 and group 1, and group 3 and group 1, in the intention-to-treat population. Secondary outcomes included safety and quality of life, which were assessed among all patients who began at least 1 cycle of chemotherapy.
A total of 1566 patients were randomly assigned between June 6, 2011, and November 28, 2014, including 522 patients to group 1, 523 to group 2, and 521 to group 3. Of those enrolled in the study, there was a median age of 62 years (range, 54-68). There were 1073 patients (69%) with high-grade serous carcinoma, 1119 (71%) with stage IIIC–IV disease, and 745 (48%) who had debulking surgery prior to the time of randomization.
At the time of the data cutoff of March 31, 2020, and a median follow-up of 69 months (range, 61-75), there was no significant difference in OS observed in either comparison. The median OS in group 1 was 47.4 months (95% CI, 43.1-54.8), 54.8 months (46.6-61.6) in group 2, and 53.4 months (49.2-59.6) in group 3. For group 2 vsgroup 1, the hazard ratio was 0.87 (97·5% CI, 0.73-1.05) and for group 3 vs group 1, it was 0.91 (0.76-1.09).
Because neither group 2 nor group 3 performed better than group 1, the exploratory analysis comparing group 2 and group 3 did not take place.
Additionally, there was no significant difference in PFS observed within either comparison. In group 1, there was evidence of non-proportional hazards (P=0·037), with a restricted mean survival time of 23.9 months (97.5% CI, 22.1-25.6). In group 2, the restricted mean survival time was 25.3 months (23.6-27.1), and in group 3, it was 24.8 months (23.0-26.5).
In regard to safety, the most common grade 3 or 4 adverse events (AEs) were reduced neutrophil count (15% in group 1, 36% in group 2, and 30% in group 3), reduced white blood cell count (4% vs 16% vs 14%), and anemia (5% vs 13% vs 5%). There were no new serious AEs reported, but there were 7 treatment-related deaths observed including 2 in group 1, 4 in group 2, and 1 in group 3.