Clinical Summary: 

• Design/Population: In the randomized phase 2 CHRONO trial, patients with stage IIIB-IVA high-grade epithelial ovarian cancer who were amenable to complete surgery after 3 cycles of neoadjuvant chemotherapy were assigned to standard interval surgery or delayed surgery after 6 cycles of neoadjuvant chemotherapy.
• Key Outcomes: Delayed surgery after additional neoadjuvant chemotherapy did not significantly improve disease-free survival compared with standard interval surgery, with similar postoperative morbidity, mortality, and quality-of-life outcomes observed between treatment arms.
• Clinical Relevance: These findings suggest that extending neoadjuvant chemotherapy before surgery may be a feasible alternative strategy in highly chemosensitive advanced ovarian cancer, although no clear survival advantage was demonstrated.

Results from the 2 CHRONO trial demonstrated that delaying interval surgery until after 6 cycles of neoadjuvant chemotherapy did not significantly improve survival compared with standard interval surgery after 3 cycles of neoadjuvant chemotherapy among patients with advanced ovarian cancer.

These results were presented by Jean-Marc Classe, MD, PhD, Western Cancer Institute, Angers, France, at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In this study, 209 patients with stage IIIB-IVA high-grade epithelial ovarian cancer who previously received neoadjuvant chemotherapy and were considered amenable to complete cytoreductive surgery after 3 cycles were randomized 1:1 to either undergo complete surgery followed by 5 additional cycles of chemotherapy (n = 103) or receive 3 additional cycles of neoadjuvant chemotherapy followed by surgery and 2 additional cycles of chemotherapy (n = 106). Maintenance therapy was administered according to standard of care. The primary end point was median disease-free survival (DFS). Key secondary end points included complete cytoreduction rate, longitudinal quality of life, and postoperative morbidity and mortality. 

At a median follow-up of 40.4 months, median DFS was 20.2 months in the upfront arm and 23.4 months in the delayed arm (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.63 to 1.24; P = .48). Complete cytoreduction rates were 83.2% and 90%, respectively. Quality of life analyses demonstrated no significant differences between treatment groups, although social functioning, insomnia, and sexuality domains showed trends toward improvement in the delayed arm. Major postoperative complications within 30 days were reported in 5% of patients and 11% of patients, respectively (P = .11). No postoperative deaths reported within 30 days of surgery.

“No statistically significant difference was shown between the two arms of the study considering DFS, severe morbidity, mortality or [quality of life],” concluded Dr Classe et al. “New trials are needed for a better understanding of this alternative to interval surgery in highly chemosensitive advanced ovarian cancer patients.” 

Source: 

Ferron G, Dupre PF, Georgeac C, et al. CHRONO: A randomized phase II trial of the chronology of surgery after neoadjuvant chemotherapy for ovarian cancer. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 5505.