As reported in The New England Journal of Medicine by Robert L. Coleman, MD, of MD Anderson Cancer Center, and colleagues, the phase III trial Gynecologic Oncology Group (GOG)-0213 trial has shown no overall survival benefit with secondary surgical cytoreduction followed by chemotherapy with or without bevacizumab vs chemotherapy with or without bevacizumab alone in women with platinum-sensitive recurrent ovarian cancer.¹

Robert L. Coleman, MD

Study Details

In the open-label trial, 485 patients (256 from the United States, 211 from South Korea, 17 from Japan, 1 from Russia) with resectable disease who had received one prior line of therapy and had a platinum-free interval of at least 6 months were randomly assigned to secondary surgical cytoreduction followed by investigator-selected platinum-based chemotherapy with or without bevacizumab (n = 240) or chemotherapy with or without bevacizumab alone (n = 245). Randomization was stratified by platinum-free interval and chemotherapy.

Treatment regimens consisted of carboplatin/paclitaxel plus bevacizumab and bevacizumab maintenance (69% of the surgery group and 70% of the no-surgery group), carboplatin/gemcitabine plus bevacizumab and bevacizumab maintenance (15% and 14%), carboplatin/paclitaxel (14% and 13%), or carboplatin/gemcitabine (2% and 2%). Regimens consisted of paclitaxel at 175 mg/m², and carboplatin at AUC = 5 with or without bevacizumab at 15 mg/kg every 3 weeks for 6 cycles followed by maintenance bevacizumab at 15 mg/kg every 3 weeks until disease progression, unacceptable toxicity, or patient withdrawal. A subsequent protocol amendment permitted selection of either paclitaxel/carboplatin or gemcitabine at 1,000 mg/² on days 1 and 8 every 3 weeks plus carboplatin AUC = 4 every 3 weeks with or without bevacizumab for 6 cycles. The primary endpoint was overall survival in the intention-to-treat population.

For the surgery vs no-surgery groups: 82% vs 86% were between the ages of 40 and 69 (15% vs 12% ≥ 70 years); 43% vs 44% were from South Korea and 54% vs 52% were from the United States; 46% vs 43% had at least two metastatic sites; 10% vs 12% had received prior bevacizumab; and the median platinum-free interval was 20.4 months vs 18.8 months.

Overall Survival

Surgery was performed in 225 patients in the surgery group; among these patients, complete gross resection was achieved in 67%. Surgery-related adverse events of grade ≥ 3 within 30 days of surgery occurred in 9% of the surgery group, with one patient dying of postoperative complications (pulmonary embolus). Overall, 8% of the surgery group received a blood transfusion, 28% underwent bowel resection, 1% had perioperative thrombosis, and none underwent repeat laparotomy.

The median time to chemotherapy initiation was 40 days in the surgery group vs 7 days in the no-surgery group. The median follow-up was 48.1 months. The 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%. The 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 more than 12 months (HR = 1.43, 95% CI = 1.03–2.00).

Significantly poorer overall survival was observed among patients treated with surgery vs those treated with chemotherapy alone 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 who underwent 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 the surgery group with complete gross resection vs the chemotherapy-alone group (HR = 1.03, 95% CI = 0.74–1.46); a significant difference was observed in progression-free survival (HR = 0.62, 95% CI = 0.48–0.80).

Quality-of-Life Assessment

Assessment with the Trial Outcome Index of the Functional Assessment of Cancer Therapy–Ovarian showed a significant decrease in quality of life and physical functioning immediately after surgery in the surgery group. No significant interaction between treatment group and time point was observed, and no significant differences between groups in terms of quality of life was observed after recovery from surgery.

In addition to the surgery-related death in a patient in the surgery group, two deaths in the no-surgery group were considered possibly related to treatment (cardiopulmonary arrest).

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: Dr. Coleman has served as a consultant or advisor to AbbVie/Stemcentrx, AstraZeneca/MedImmune, Clovis Oncology, Esperance Pharmaceuticals, GamaMabs Pharma, Genentech/Roche, Genmab, the National Comprehensive Cancer Network, Oncolytics, OncoMed, Sotio, and Tesaro; has received research funding from Abbott/AbbVie, Array BioPharma, AstraZeneca/MedImmune, Clovis Oncology, Esperance Pharmaceuticals, Johnson & Johnson, Merck, OncoMed, and Roche/Genentech; and has been reimbursed for travel, accommodations, or expenses by AstraZeneca/MedImmune, Array BioPharma, Clovis Oncology, Gynecologic Oncology Group, Merck, Research to Practice, Roche/Genentech, Sotio, and Vaniam Group.

REFERENCE

1. Coleman RL, Spirtos NM, Enserro D, et al: Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med 381:1929-1939, 2019.