Weekly Dose-Dense Paclitaxel in Ovarian Cancer: ICON8 Trial
Posted: Friday, December 20, 2019
Incorporation of weekly dose-dense paclitaxel is feasible, although it does not seem to improve progression-free survival rates for non-Japanese women with ovarian cancer, according to Andrew R. Clamp, PhD, of The Christie National Health Service Foundation Trust, and colleagues. This finding from the ICON8 trial, which contrasts with that of studies showing improved survival outcomes in Japanese women with advanced ovarian cancer, was published in The Lancet.
“Weekly dose-dense paclitaxel should no longer be recommended as a component of first-line epithelial ovarian cancer treatment for women of non-Japanese ethnic origin,” the authors concluded. “Because potential ethnic pharmacogenomic differences might affect the efficacy and toxicity of paclitaxel, dose-dense paclitaxel could remain a first-line treatment option for Japanese women with ovarian cancer.”
This multicenter, phase III trial included 1,566 women with ovarian cancer, from the United Kingdom, Australia, New Zealand, Mexico, South Korea, and the Republic of Ireland. They were randomly assigned to receive standard carboplatin and paclitaxel every 3 weeks (group 1), standard carboplatin every 3 weeks and a lower dose of paclitaxel weekly (group 2), or a lower dose of carboplatin and paclitaxel weekly (group 3). More than 85% of patients completed at least six cycles of platinum-based chemotherapy.
Paclitaxel dose intensification did not result in significant improvement in progression-free survival in group 2 or 3 compared with group 1 (restricted mean survival time of 24.9 and 25.3 months, vs. 24.4 months, respectively); the median progression-free survival rates also did not increase (20.8 and 21.0 months, vs. 17.7 months).
Toxicities among the three groups were similar, but weekly paclitaxel treatment led to an increase in grade 3 and 4 adverse events. Neutropenia accounted for the main increase in toxicity for patients in group 2 or 3. Of note, despite the increased paclitaxel dose in two treatment arms, no significant differences in the incidence of sensory neuropathy (grade 2 or higher) were reported between treatment groups.
Disclosure: For full disclosures of the study authors, visit thelancet.com.
