Three-Weekly Regimen Remains First-Line Standard of Care For Epithelial Ovarian Cancer

Results from the ICON8 trial support the continued use of a 3-weekly regimen of carboplatin and paclitaxel for epithelial cancer of the ovaries or fallopian tubes, or primary peritoneal carcinoma

medwireNews: The ICON8 study, presented at the ESMO Congress 2017 in Madrid, Spain, shows no significant survival or surgical benefit with dose-dense weekly carboplatin plus paclitaxel versus the standard 3-weekly regimen for patients with treatment-naïve epithelial ovarian or fallopian tube cancer or primary peritoneal carcinoma (EOC).

Presenting author Andrew Clamp, from Christie NHS Foundation Trust and The University of Manchester in the UK, explained that the phase III trial was designed to test the benefit of weekly paclitaxel in a predominantly European population after the JGOG 3016 study in Japanese women showed improved progression-free survival (PFS) and overall survival (OS) with a weekly dose-dense strategy.

ICON8 was open to patients with stage Ic/IIa disease with high-grade histology or stage IIb/IV with any histology, and an ECOG performance status of 0–2. None of the patients had previously received systemic therapy for EOC or had planned maintenance therapy.

In all, 522 women were randomly assigned to receive six cycles of the standard 3-weekly schedule of carboplatin dosed to an area under the concentration–time curve (AUC) 5 plus paclitaxel 175 mg/m2. A further 522 patients were randomly assigned to receive six cycles of the same carboplatin regimen but paclitaxel given at a weekly dose of 80 mg/m2, while 521 patients were assigned to receive weekly doses of carboplatin to AUC 2 and paclitaxel 80 mg/m2.

PFS did not significantly differ between the three treatment groups, at a median of 17.9 months with the 3-weekly schedule, 20.6 months for 3-weekly carboplatin plus weekly paclitaxel and 21.1 months for both drugs given weekly.

Nor did PFS significantly differ between the trial arms for patients who underwent immediate primary surgery (median 49.3, 43.2 and 43.7 months, respectively) or those who were scheduled to undergo delayed primary surgery after three cycles of treatment (13.8, 14.6 and 15.4 months, respectively). Among the latter patients, surgery was performed after 3 weeks in 73%, 77% and 86% of the trial groups, respectively.

OS data are yet to mature, with only 58% of the 602 events required for the full analysis having occurred, Andrew Clamp told the congress. But at last measurement median OS was similar across the groups, at 46.5 months for the 3-weekly regimen, 48.1 months for 3-weekly carboplatin plus weekly paclitaxel and 54.0 months with weekly carboplatin and paclitaxel. Two-year survival was reached by 80%, 82% and 78% of patients, respectively.

The presenter summarised that weekly dose-dense paclitaxel allows a higher intensity of the agent and is well tolerated by the European patient population, without adversely affecting timely interval surgery.

Grade 3–4 toxicity was slightly higher with weekly paclitaxel and weekly carboplatin and paclitaxel than the standard schedule, affecting 63% and 53% of patients versus 42% but this was attributed to uncomplicated haematological toxicity.

Nevertheless, the dose-dense strategy did not significantly improve survival outcomes or affect surgical outcome in the patients, with 60%, 57% and 51% of patients achieving debulking without visible residual disease.

Andrew Clamp therefore concluded: “Three-weekly carboplatin–paclitaxel scheduling remains the standard of care chemotherapy component of first-line ovarian cancer treatment.”

He also suggested in a press release that the difference in outcome between the Japanese and European patients might be accounted for by pharmacogenomic differences in the ethnic group, adding that “it remains appropriate to continue to offer weekly dose-dense paclitaxel as a treatment option to Japanese women.”


Clamp A, McNeish I, Dean A, et al. 929O_PR. ICON8: A GCIG phase III randomised trial evaluating weekly dose- dense chemotherapy integration in first-line epithelial ovarian/fallopian tube/primary peritoneal carcinoma (EOC) treatment: Results of primary progression- free survival (PFS) analysis. ESMO 2017 Congress; 8–11 September: Madrid Spain.

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