In the phase III Gynecologic Cancer Intergroup ICON8 trial reported in The Lancet, Clamp et al found that first-line weekly dose-dense chemotherapy did not improve progression-free survival vs standard 3-weekly chemotherapy in a predominantly European population with epithelial ovarian cancer.

Study Details

The trial included 1,566 women with newly diagnosed International Federation of Gynecology and Obstetrics stage IC to IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Patients were randomly assigned between June 2011 and November 2014 to receive six cycles of:

• Standard carboplatin at AUC 5 or 6 and 175 mg/m² of paclitaxel every 3 weeks (group 1, n = 522)
• Carboplatin at AUC 5 or 6 every 3 weeks and 80 mg/m² of paclitaxel weekly (group 2, n = 523), or
• Carboplatin at AUC 2 and 80 mg/m² of paclitaxel weekly (group 3, n = 521).

Patients could have had primary cytoreductive surgery, could receive chemotherapy for planned secondary cytoreductive surgery, or have no planned surgery. A total of 89% of patients in each group were from the United Kingdom; others were from Korea, Ireland, Australia/New Zealand, and Mexico.

The co-primary endpoints were progression-free survival and overall survival in the intention-to-treat population, with the main comparisons being between the group 1 control group and the two weekly dose-dense groups.

Progression-Free Survival

Median follow-up was 36.4 months. Median progression-free survival was 17.7 months in the control group vs 20.8 months in group 2 (weekly paclitaxel; P = .35) and 21.0 months in group 3 (weekly carboplatin/paclitaxel; P = .51). Restricted mean survival time was 24.4 months, 24.9 months, and 25.3 months.

Overall survival results are not yet mature. Estimated overall survival at 2 years was 80%, 82%, and 78%, respectively.  

Toxicity

Grade 3 or 4 adverse events occurred in 42% of patients in group 1, 62% of group 2, and 53% of group 3, with the major difference from the control group being a higher incidence of uncomplicated neutropenia in the two dose-dense groups (15% vs 35% and 30%). Febrile neutropenia occurred in 4%, 6%, and 3% of patients. Sensory neuropathy of grade ≥ 2 occurred in 27%, 24%, and 22% of patients.

The investigators concluded, “Weekly dose-dense chemotherapy can be delivered successfully as first-line treatment for epithelial ovarian cancer but does not significantly improve progression-free survival compared with standard 3-weekly chemotherapy in predominantly European populations.”

Elizabeth C. James, MSc, of the Medical Research Council Clinical Trials Unit at UCL, is the corresponding author for The Lancet article.

Disclosure: The study was funded by Cancer Research UK, Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, and Cancer Australia. For full disclosures of the study authors, visit thelancet.com.