Neoadjuvant Chemotherapy vs Upfront Debulking Surgery in Advanced Tubo-Ovarian Cancer
As reported in The Lancet Oncology by Vergote et al, a pooled analysis of individual patient data in long-term follow-ups of the phase III EORTC 55971 and CHORUS trials indicated that overall survival is similar with neoadjuvant therapy vs upfront debulking surgery in advanced tubo-ovarian cancer. Neoadjuvant therapy was associated with better outcomes in stage IV disease. The prior primary reports from the two trials showed similar outcomes with the two approaches.
Study Details
The study was a per-protocol pooled analysis including 1,220 women—670 from the EORTC trial and 550 from the CHORUS trial. Of these, 612 women were randomly allocated to receive upfront debulking surgery followed by at least 6 courses of platinum-based chemotherapy, and 608 were randomly allocated to receive 3 courses of neoadjuvant platinum-based chemotherapy followed by interval debulking surgery followed by at least 3 additional courses of platinum-based chemotherapy.
In the EORTC trial, women had International Federation of Gynecology and Obstetrics (FIGO) stage IIIC or IV invasive epithelial tubo-ovarian carcinoma. Inclusion criteria in the CHORUS trial were similar, with women with stage IIIA and IIIB disease also being eligible.
The median size of the largest metastatic tumor at diagnosis was 8 cm. Overall, 55 women (5%) had stage II–IIIB disease, 831 (68%) had stage IIIC disease, and 230 (19%) had stage IV disease. Stage data were missing for 104 (9%).
Survival Outcomes
Median follow-up was 7.6 years among all patients, including 9.2 years in the EORTC trial and 5.9 years in the CHORUS trial. In the entire population, median overall survival was 27.6 months in the neoadjuvant chemotherapy group vs 26.9 months in the upfront debulking surgery group (hazard ratio [HR] = 0.97, P = .586). Median progression-free survival was 11.6 months vs 11.1 months (HR = 0.98, P = .688).
Median overall survival was 30.2 months for all patients in the EORTC trial vs 23.6 months for all in the CHORUS trial (HR = 1.20, P = .004), but the test for heterogeneity was not significant (P = .17). Median progression-free survival was similar in the two trials (11.5 vs 10.9 months, HR = 0.96, P = .531). Among women with stage IV disease, those in the neoadjuvant chemotherapy group had better median overall survival (24.3 vs 21.2 months, HR = 0.76, P = .048) and progression-free survival (10.6 vs 9.7 months, HR = 0.77, P = .049).
The investigators concluded, “Long-term follow-up data substantiate previous results showing that neoadjuvant chemotherapy and upfront debulking surgery result in similar overall survival in advanced tubo-ovarian cancer, with better survival in women with stage IV disease with neoadjuvant chemotherapy. This pooled analysis, with long-term follow-up, shows that neoadjuvant chemotherapy is a valuable treatment option for patients with stage IIIC–IV tubo-ovarian cancer, particularly in patients with a high tumor burden at presentation or poor performance status.”
The study was funded by the National Cancer Institute and Flemish League Against Cancer.
Ignace Vergote, MD, of University Hospitals Leuven, Leuven Cancer Institute, is the corresponding author for The Lancet Oncology article.
Disclosure: See study authors’ full disclosures at thelancet.com.
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