Efficacy
After a median follow-up of 22.3 months, the median PFS was 17.3 months (95% CI 15.2 - 20.2) in patients assigned to treatment every 3 weeks, versus 18.3 months (95% CI 16.8 - 20.9) in women allocated to the weekly schedule (HR 0.96, 95% CI 0.80-1.16; p=0.66).r
FACT-O/TOI scores differed significantly between the two schedules (treatment-by-time interaction p < 0.0001); with treatment given three weekly FACT-O/TOI scores worsened with every cycle; whereas for the weekly schedule, after a transient worsening at week 1, FACT-O/TOI scores remained stable.
Kaplan-Meier survival analysis: (A) Progression-free survival (B) Overall survival
© Lancet Oncology 2014
Forrest Plot showing treatment effect on PFS in sub-groups
© Lancet Oncology 2014
Co-primary end-point analysis of FACT-O/TOI scores
© Lancet Oncology 2014
The trial shows administration of weekly carboplatin and paclitaxel augments QoL and has a better toxicity profile than the 3-weekly schedule; however it does not significantly improve PFS.
The dosing schedule may be a reasonable alternative for first-line treatment of advanced ovarian cancer in selected patients in clinical practice.
The results of the ICON-8 trial confirmed that weekly paclitaxel or weekly paclitaxel/carboplatin regimens were not superior to the 3-weekly regimen with no improvement in PFS. After a median follow-up of 36.8 month, PFS with 3-weekly regimen was 17.7 months (IQR 10.6–not reached) vs 20.8 months (IQR 11.9–59.0; p=0.35) and 21.0 months (IQR 12.0–54.0; p=0.51) with weekly paclitaxel and weekly paclitaxel/carboplatin regimens, respectively.r As QoL in the first 9 months was significantly better in the three-weekly group, routine use of weekly therapy is not recommended for general use.r
GINECO/GCIG trial compared feasibility, safety and efficacy of 3-weekly carboplatin plus paclitaxel, weekly carboplatin plus paclitaxel (administered on days 1, 8, and 15 every 4 weeks) and 3-weekly single-agent carboplatin in elderly (age ≥ 70 years) frail (GVS score ≥ 3) patients with FIGO stage III/IV epithelial ovarian cancer.r After a median follow-up of 12.7 months, PFS was significantly shorter in the single-agent carboplatin arm compared to the 3-weekly doublet arm (HR 2.51, 95% CI 1.56-4.04; p < 0.001). The OS showed a similar pattern (HR 2.79, 95% CI 1.57-4.96; p < 0.001). However, there were no significant differences in PFS (12.5 months, 95% CI 10.3-15.3 vs 8.3 months, 95% CI 6.6-15.3; p=0.12; respectively) or OS (17.3 months, 95% CI 10.8-32.2 vs not-reached, 95% CI 21.0-32.3, p=0.16) in weekly and 3-weekly doublet arms. Treatment-related toxicities were less common in 3-weekly combination group (43%) than single-agent carboplatin or weekly combination therapy (both 58%). However, toxicity-related treatment discontinuation was similar in the 3 treatment groups (20%, 15% and 23%, respectively).