Vergote I, et al. - Researchers examined the effectiveness of neoadjuvant chemotherapy vs debulking surgery in advanced tubo-ovarian cancers via analyzing individual patient data from two randomized trials comparing the two-treatment strategy. Outcomes suggest similar overall survival in advanced tubo-ovarian cancer using neoadjuvant chemotherapy vs upfront debulking surgery, with better survival in women with stage IV disease with neoadjuvant chemotherapy. This pooled analysis with long-term follow-up demonstrates the efficacy of neoadjuvant chemotherapy as a valuable option for patients with stage IIIC–IV tubo-ovarian cancer, especially in patients with a high tumor burden at presentation or poor performance status.

Methods

• Individual patient data from the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial (NCT00003636) and the Medical Research Council Chemotherapy Or Upfront Surgery (CHORUS) trial (ISRCTN74802813) were per-protocol pooled analyzed.
• Women with biopsy-proven International Federation of Gynecology and Obstetrics (FIGO) stage IIIC or IV invasive epithelial tubo-ovarian carcinoma were included in the EORTC trial.
• The CHORUS trial had inclusion criteria similar to those of the EORTC trial, and in addition, it included women with apparent FIGO stage IIIA and IIIB disease.
• Using the reverse Kaplan-Meier method, researchers sought to demonstrate non-inferiority in overall survival with neoadjuvant chemotherapy compared with upfront debulking surgery in this pooled analysis.
• Cochran's Q heterogeneity statistic was used for tests for heterogeneity.

Results

• The pooled analysis included data for 1,220 women, 670 from the EORTC trial and 550 from the CHORUS trial.
• Random allocation of 612 women to receive upfront debulking surgery and 608 to receive neoadjuvant chemotherapy was performed.
• Median follow-up of 7.6 years was performed (IQR 6.0–9.6; EORTC, 9.2 years [IQR 7.3–10.4]; CHORUS, 5.9 years [IQR 4.3–7.4]).
• Median age was 63 years (IQR 56–71); the largest metastatic tumor had median size of 8 cm (IQR 4.8–13.0) at diagnosis.
• FIGO stage II–IIIB disease was noted in 55 (5%) women, stage IIIC disease in 831 (68%), and stage IV disease in 230 (19%); staging data was missing for 104 (9%) women.
• Patients who underwent neoadjuvant chemotherapy and upfront debulking surgery displayed no difference in median overall survival (27.6 months [IQR 14.1–51.3] and 26.9 months [12.7–50.1], respectively; hazard ratio [HR] 0.97, 95% CI 0.86–1.09; p=0.586).
• The EORTC and CHORUS patients had significantly different median overall survival at 30.2 months (IQR 15.7–53.7) and 23.6 months (10.5–46.9), respectively (HR 1.20, 95% CI 1.06–1.36; p=0.004), but it was not heterogeneous (Cochran's Q, p=0.17).
• Neoadjuvant chemotherapy led to significantly better outcomes compared with upfront debulking surgery among women with stage IV disease (median overall survival 24.3 months [IQR 14.1–47.6] and 21.2 months [10.0–36.4], respectively; HR 0.76, 95% CI 0.58–1.00; p=0.048; median progression-free survival 10.6 months [7.9–15.0] and 9.7 months [5.2–13.2], respectively; HR 0.77, 95% CI 0.59–1.00; p=0.049).