Weekly First-Line Dose-Dense Chemo Did Not Improve Survival Vs Standard 3-Weekly Chemo in Epithelial Ovarian Cancer

Results from the phase 3 ICON8 trial showed patients with epithelial ovarian cancer did not experience an overall survival or progression-free survival benefit with weekly dose-dense chemotherapy in the first line compared with 3 times weekly.

Weekly dose-dense chemotherapy in the first-line setting did not improve survival compared with standard 3-weekly chemotherapy in patients with epithelial ovarian cancer and does not have a place within a standard frontline multimodal strategy, according to findings from the phase 3 ICON8 trial (NCT01654146) published in The Lancet Oncology.

In the control group or group 1—in which patients were treated with 3-weekly carboplatin at 175mg/m2 on day 1 of each 21-day cycle for 6 cycles—the median overall survival (OS) was 47.4 months (95% CI, 43.1-54.8). In group 2 or the weekly paclitaxel group—which included a treatment of carboplatin and dose-fractionated paclitaxel at 80 mg/m2on days 1, 8, and 15 of each cycle for 6 cycles—the median OS was 54.8 months (95% CI, 46.6-61.6). Lastly, in group 3—the treatment of which was weekly dose-fractionated carboplatin and paclitaxel at 80 mg/m2on days 1, 8, and 15 every cycle for 6 cycles—the median OS was 53.4 months (95% CI, 49.2-59.6).

When comparing group 1 vs group 2, the HR was 0.87 (97.5% CI, 0.73-1.05), and for group 3 vs group 1, the HR was 0.91 (97.5% CI, 0.76-1.09). Investigators reported observing no difference in progression-free survival (PFS) across all groups (P = .037). The restricted mean survival time in group 1 was 23.9 months (97.5% CI, 22.1-25.6), 25.3 months (97.5% CI, 23.6-27.1) in group 2, and 24.8 months (97.5% CI, 23.0-26.5) in group 3.

A total of 1566 patients enrolled on the trial and were randomly assigned to either group 1 (n = 522), group 2 (n = 523), or group 3 (n =521). The median age was 62 years. In total, 69% of patients had high-grade serous carcinoma and 71% had stage IIIC to IV disease. Prior to chemotherapy, 48% of patients received debulking surgery and began treatment a median of 36 days after surgery. Delayed surgery was planned for 50% of patients, and 3% were not candidates for future surgical intervention following a multidisciplinary team review. In less than 1% of patients, treatment had not begun because of rapid clinical deterioration, and 2% of patients withdrew from the trial before the final analysis.

The median follow-up was 69 months, during which 62% of patients in group 1, 59% in group 2, and 60% in group 3 had died. Investigators were not able to uncover evidence of non-proportional hazards for OS (P = .84). Moreover, progression was reported to have occurred I 75% of patients in group 1, 75% in group 2, and 74% in group 3 at the data cut-off.

The subgroup analysis assessed the impact of weekly chemotherapy on survival among those who received either immediate primary surgery or delayed primary surgery. The median OS for patients who received delayed primary surgery was 32.0 months (95% CI, 30.3-35.5) in group 1, 38.6 months (95% CI, 35.8-42.3) in group 2, and 37.2 months (95% CI, 32.6-43.6) in group 3. For those who received immediate primary surgery, the median OS was 78.6 months (95% CI, 71.0-not reached [NR]) in group 1, 93.6 months (95% CI, 77.1-NR) in group 2, and 85.8 months (95% CI, 72.9-NR) in group 3. During follow-up, progression occurred in 56% of patients who had immediate primary surgery and 91% who had delayed primary surgery.

In group 1, 42% of patients had at least 1 grade 3 or higher adverse effect (AE), compared with 62% in group 2 and 53% in group 3. The most common grade 3 or worse AEs included decreased neutrophil counts (15% vs 36% vs 30%), reduced white blood cell count (4% vs 16% vs 14%), and anemia (5% vs 13% vs 5%) in groups 1, 2, and 3, respectively. Sensory neuropathy of grade 2 or higher occurred across all groups. Patients did not experience any new drug-related serious AEs, and 7 patients had treatment-related deaths.

Reference

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. 2022;23(7):919-930. doi:10.1016/S1470-2045(22)00283-2