Ovarian cancer: weekly dose-dense paclitaxel fails phase 3 European study

  • Clamp AR & et al.
  • Lancet
  • 29 Nov 2019

  • curated by Deepa Koli
  • Univadis Clinical Summaries
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Takeaway

  • Weekly dose-dense paclitaxel-based chemotherapy is feasible but fails to extend PFS in predominantly European patients with ovarian cancer vs chemotherapy administered every 3 weeks (3-weekly chemotherapy).

Why this matters

  • The Japanese JGOG3016 trial showed a significant survival advantage with dose-dense weekly paclitaxel and 3-weekly carboplatin.

Study design

  • Phase 3 ICON8 trial of 1566 women with newly diagnosed International Federation of Gynecology and Obstetrics stage IC-IV epithelial ovarian cancer.
  • Patients were randomly assigned to 3-weekly carboplatin-paclitaxel (group 1), 3-weekly carboplatin and weekly dose-dense paclitaxel (group 2), or weekly carboplatin with weekly dose-dense paclitaxel (group 3).
  • Funding: Cancer Research UK; Medical Research Council; others.

Key results

  • Compared with 3-weekly carboplatin-paclitaxel, median total paclitaxel dose was higher in the weekly dose-dense groups (1010 vs 1233 and 1274 mg/m2).
  • 65% of patients experienced disease progression.
  • No significant difference in median PFS was observed in group 1 vs group 2 (17.7 vs 20.8 months; P=.35) and vs group 3 (vs 21.0 months; P=.51).
  • Grade 3-4 adverse were higher in groups 2 and 3 vs 1 (62% and 53% vs 42%).
    • Uncomplicated neutropenia was a major contributor for higher grade 3-4 toxicities (35% and 30% vs 15%).
  • Incidences of febrile neutropenia and sensory neuropathy were similar across groups.

Limitations

  • Open-label design.