In the phase III trial Gynecologic Oncology Group (GOG)-0213 trial, reported in The New England Journal of Medicine by Robert L. Coleman, MD, and colleagues, no overall survival benefit was found for secondary surgical cytoreduction followed by chemotherapy vs chemotherapy alone in women with platinum-sensitive recurrent ovarian cancer.

Robert L. Coleman, MD

Study Details

The open-label trial included 485 patients (from the United States and South Korea; patients from South Korea accounted for nearly half the trial population) with resectable disease who had received one prior line of therapy. They were randomly assigned to secondary surgical cytoreduction followed by platinum-based chemotherapy (n = 240) or chemotherapy alone (n = 245).

Patients had to have a platinum-free interval of 6 months or more in order to be enrolled. Chemotherapy regimens consisted of carboplatin/paclitaxel plus bevacizumab and bevacizumab maintenance (69% of surgery group and 70% of no-surgery group), carboplatin/gemcitabine plus bevacizumab and bevacizumab maintenance (15% and 14%), carboplatin/paclitaxel (14% and 13%), or carboplatin/gemcitabine (2% and 2%). The primary endpoint was overall survival in the intention-to-treat population.

Overall Survival Results

Secondary cytoreduction was performed in 225 patients in the surgery group; among these, complete gross resection was achieved in 67%. Surgical morbidity at 30 days was 9%, with one patient (0.4%) dying from postoperative complications. The median time to chemotherapy initiation was 40 days in the surgery-plus-chemotherapy group vs 7 days in the chemotherapy-alone group.

Median follow-up was 48.1 months. Median overall survival was 50.6 months in the surgery-plus-chemotherapy group vs 64.7 months in the chemotherapy group (hazard ratio [HR] = 1.29, 95% confidence interval [CI] = 0.97–1.72, P = .08). Overall survival at 3 years was 67% vs 74%. Median progression-free survival was 18.9 months vs 16.2 months (HR = 0.82, 95% CI = 0.66–1.01), with 3-year rates of 29% vs 20%.

In subgroup analyses, no significant differences in overall survival were observed according to enrollment in the United States (HR = 1.45, 95% CI = 1.05–2.00) or South Korea (HR = 0.97, 95% CI = 0.53–1.79); receipt of carboplatin/paclitaxel plus bevacizumab (HR = 0.95, 95% CI =  0.65–1.38) or carboplatin/gemcitabine plus bevacizumab (HR = 1.89, 95% CI = 0.93–3.86); or platinum-free interval of 6 to 12 months (HR = 0.92, 95% CI = 0.54–1.56) or longer than 12 months (HR = 1.43, 95% CI = 1.03–2.00). 

Significantly poorer overall survival was observed among patients in the surgery group vs patients in the chemotherapy-alone group who did not receive bevacizumab (HR = 2.26, 95% CI = 1.31–3.88). In regard to this finding, the authors stated, “Although a detriment in overall survival was observed among those undergoing surgery but not receiving bevacizumab, it is unknown whether patients not receiving bevacizumab … were less likely to receive it in subsequent lines of therapy; such an imbalance could affect long-term outcomes.”

Compared with patients in the surgery group without complete gross resection (n = 89), those with complete gross resection (n = 150) had longer overall survival (median = 56.0 vs 37.8 months; HR = 0.61, 95% CI = 0.40–0.93) and progression-free survival (median = 22.4 vs 13.1 months; HR = 0.51, 95% CI = 0.36–0.71). No significant difference in overall survival was observed between surgery group patients with complete gross resection vs the chemotherapy-alone group (HR = 1.03, 95% CI = 0.74–1.46), but a significant difference was observed in progression-free survival (HR = 0.62, 95% CI = 0.48–0.80).

Patients who underwent cytoreductive surgery reported a significant decline in quality of life and patient-reported outcomes immediately after the procedure. By 6 weeks, they reached parity with patients who did not undergo surgery, and they maintained parity at subsequent assessments.

The authors concluded, “In this trial involving patients with platinum-sensitive, recurrent ovarian cancer, secondary surgical cytoreduction followed by chemotherapy did not result in longer overall survival than chemotherapy alone.”

Disclosure: The study was funded by the National Cancer Institute and others. For full disclosures of the study authors, visit nejm.org.