First-Line Weekly Dose-Dense Chemotherapy Not Recommended for Epithelial Ovarian Cancer

Women with epithelial ovarian cancer treated with once a week (1-weekly) dose-dense chemotherapy experienced no significant improvement in overall survival (OS) and progression-free survival (PFS) compared to women treated once every 3 weeks (3-weekly), according to a phase 3 trial.

“The JGOG 3016 trial reported significant improvement in [PFS] and [OS] with dose-dense weekly paclitaxel and 3-weekly (ie, once every 3 weeks) carboplatin,” wrote lead author Andrew Clamp, PhD, The Christie NHS Foundation Trust and University of Manchester, Manchester, UK, and coauthors. “However, this benefit was not observed in the previously reported [PFS] results of ICON8,” they added.

The phase 3 trial compared first-line 1-weekly dose-dense chemotherapy vs the standard 3-weekly treatment in 1566 women with newly diagnosed ovarian cancer. Patients were randomized in a 1:1:1 ratio to 3 groups: 3-weekly carboplatin and 3-weekly paclitaxel (n = 522); control; group 1), 3-weekly carboplatin and weekly paclitaxel (n = 523; group 2), and weekly carboplatin paclitaxel (n = 521; group 3). Primary outcomes were OS and PFS.

The median follow-up was 69 months with no observed difference in OS between the groups. Median OS was 47.4 months (95% confidence interval [CI], 43.1 to 54.8) for group 1, 54.8 months (95% CI, 46.6 to 61.6) for group 2, and 53.4 months (95% CI, 49.2 to 59.6) for group 3. In addition, no difference in PFS was observed between the groups, with a mean PFS of 23.9 months (97.5% CI, 22.1 to 25.6) in group 1, 25.3 months (97.5% CI, 23.6 to 27.1) in group 2, and 24.8 months (97.5% CI, 23 to 26.5) in group 3.

The most common grade 3 to 4 adverse events (AEs) included reduced neutrophil count, reduced white blood cell, and anemia. Researchers reported no new serious AEs. There were 7 treatment-related deaths.

“We found that first-line weekly dose-dense chemotherapy did not improve overall or progression-free survival compared with standard 3-weekly chemotherapy and should not be used as part of standard multimodality front-line therapy in this patient group,” concluded Dr Clamp and colleagues.

Source:

Clamp AR, James EC, McNeish IA, et al. Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal cancer treatment (ICON8): overall survival results from an open label, randomised, controlled, phase 3 trial. Lancet Oncol. Published online  June 8, 2022. doi:10.1016/S1470-2045(22)00283-2