Six NACT Cycles Before Surgery Fail to Improve DFS in Advanced Ovarian Cancer

Surgery after 6 cycles of neoadjuvant chemotherapy (NACT) did not improve outcomes nor meet the primary end point of disease-free survival (DFS) compared with surgery after 3 cycles of NACT among patients with advanced high-grade epithelial ovarian cancer, according to results from the phase 2 CHRONO trial (NCT03579394) shared at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

At a median follow-up of 40.4 months (range, 0.03–72.7), median DFS was 23.4 months (95% CI, 19.0–30.4) in the 6-cycle arm vs 20.2 months (95% CI, 18.2–23.6) in the 3-cycle arm, a difference that was not statistically significant (HR, 0.88; 95% CI, 0.63–1.24; log-rank P = .4782). A total of 133 DFS events had been observed at the data cutoff of June 30, 2025.

Secondary survival outcomes were consistent with the primary result. At a medium follow-up of 44.1 months (0.03-69.7), the median time for subsequent treatment (TFST) was 26.3 months (95% CI, 22.5–31.3) with 6 NACT cycles vs 24.8 months (95% CI, 21.5–34.4) with 3 cycles, with no significant difference between arms (HR, 1.04; 95% CI, 0.74–1.47; P = .8179). Overall survival (OS) data remained immature; at a median OS follow-up of 45.6 months, median OS was 60.0 months (95% CI, 44.4–not evaluable [NE]) in the 6-cycle arm vs 50.5 months (95% CI, 45.5–64.2) in the 3-cycle arm, also without statistical significance (HR, 0.83; 95% CI, 0.54–1.28; P = .3899). Data maturity did not allow reliable estimation of median OS in either arm.

“The CHRONO trial did not report any superiority of surgery after 6 cycles of NACT compared with surgery after 3 cycles, in terms of DFS, TFST, OS, post-operative mortality, severe morbidity, nor [quality of life (QoL)] with a trend in favor of [delayed cytoreductive surgery (DCS)] regarding social functioning, sexuality, and insomnia,” wrote lead study author Jean-Marc Classe, MD, of Institut de Cancérologie de l'Ouest and GINECO in Saint-Herblain, France, and coauthors.

The multicenter open-label trial enrolled 209 patients with FIGO stage III to IVA high-grade epithelial ovarian cancer who were not amenable to complete upfront surgery but were eligible for complete surgery following 3 platinum-based NACT cycles. Eligible patients also had an age of 18 years or older and an ECOG performance status of 0 or 1.

Patients were randomly assigned 1:1 to either arm A (n = 103) or arm B (n = 106). Patients in arm A proceeded directly to interval cytoreductive surgery (ICS) after 3 NACT cycles, followed by 5 additional cycles of chemotherapy plus maintenance according to standard of care. Those in arm B received 3 additional NACT cycles before DCS, then 2 additional cycles of chemotherapy and maintenance according to standard of care.

The primary end point was DFS, powered at 85% to detect an improvement from a median of 10 months (HR, 0.59); secondary endpoints included OS, TFST, QoL, postoperative mortality, and severe morbidity.

Postoperative mortality within 30 days was 0% in both arms. Grade 3 or 4 postoperative adverse events within 30 days were numerically higher with DCS than with ICS (11% vs 5%). Total grade 3 or 4 adverse events were similar across arms (41.5% vs 40.8%), though surgery-related grade 3 or 4 events were more frequent in the DCS arm (13.2% vs 5.8%) and chemotherapy-related grade 3/4 events were more common in the ICS arm (27.2% vs 19.8%). Complete surgery with no residual disease was achieved in 90.0% of patients in the DCS arm vs 83.2% in the ICS arm.

QoL was assessed using the EORTC QLQ-C30 and ovarian cancer–specific OV28 modules. No statistically significant between-arm differences were observed in global health status, functional subscales, or symptom domains on either instrument; numerical trends favored the DCS arm in social functioning, sexuality, and insomnia.

The presenters noted that the trial's main limitation was a control-arm DFS assumption lower than the DFS ultimately observed in the 3-cycle surgery group, suggesting the study may have been underpowered given better-than-expected outcomes in the standard-of-care arm. Investigators concluded that CHRONO did not support delayed surgery after 6 NACT cycles over interval surgery after 3 cycles in any assessed outcome and called for further studies to identify which patients—based on tumor biology and chemosensitivity—may benefit from the extended NACT approach.

References

Ferron G, Dupre PF, Georgeac C, et al. CHRONology of surgery after Neoadjuvant chemotherapy treatment for Ovarian cancer: the CHRONO randomized phase II trial. J Clin Oncol. 2026;44(suppl 16):5505. doi:10.1200/JCO.2026.44.16_suppl.5505