In randomised, phase III GOG-0213 study that involved patients with platinum-sensitive, recurrent epithelial ovarian cancer, secondary surgical cytoreduction followed by chemotherapy did not result in longer overall survival (OS) than chemotherapy alone. The results are published by Dr. Robert Coleman of the University of Texas M.D. Anderson Cancer Center in Houston, TX, US and colleagues on 14 November 2019 in The New England Journal of Medicine.
The authors wrote in the study background that secondary surgical cytoreduction is widely practiced in women with platinum-sensitive, recurrent epithelial ovarian, primary peritoneal, or fallopian-tube cancer, but it has not been evaluated in phase III trial.
Given the widespread adoption of primary surgical cytoreduction, it is not surprising that the approach is also strongly considered for patients with recurrent disease, particularly those who are considered to be candidates for platinum reinduction and those with isolated or limited-volume recurrent disease. However, there is no supporting evidence from randomised trial.
Furthermore, with the availability of bevacizumab and PARP inhibitors as maintenance treatment with proven progression-free survival (PFS) benefit in patients with platinum-sensitive, recurrent ovarian cancer who have a response to salvage therapy, it is important to clarify the role of secondary cytoreductive surgery.
GOG-0213 investigators randomly assigned patients with recurrent ovarian cancer who had received one previous therapy, had a platinum-free interval of 6 months or more, and had investigator-determined resectable disease to undergo secondary surgical cytoreduction and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Adjuvant chemotherapy, paclitaxel/carboplatin or gemcitabine/carboplatin, and use of bevacizumab were at the discretion of the investigator. The study primary endpoint was OS.
A total of 485 patients were randomised, 240 to secondary cytoreduction before chemotherapy and 245 to chemotherapy alone. The median follow-up was 48.1 months. Complete gross resection was achieved in 67% of the patients assigned to surgery who underwent the procedure. Platinum-based chemotherapy with bevacizumab followed by bevacizumab maintenance was administered to 84% of the patients overall and was equally distributed between the two groups.
The hazard ratio (HR) for death (surgery vs no surgery) was 1.29 (95% confidence interval [CI], 0.97 to 1.72; p = 0.08), which corresponded to a median OS of 50.6 months and 64.7 months, respectively. Adjustment for platinum-free interval and chemotherapy choice did not alter the effect.
The HR for disease progression or death (surgery vs no surgery) was 0.82 (95% CI, 0.66 to 1.01); median PFS, 18.9 months and 16.2 months, respectively.
Surgical morbidity at 30 days was 9%; 1 patient (0.4%) died from postoperative complications. Patient-reported quality of life decreased significantly after surgery but did not differ significantly between the two groups after recovery.
The study team concluded that secondary surgical cytoreduction in patients with platinum-sensitive, recurrent epithelial ovarian cancer appears to be feasible, with acceptable postoperative morbidity, but did not result in longer OS than no surgery. The HR for disease progression or death did not indicate that surgery plus chemotherapy was superior to chemotherapy alone.
The study was supported by the US National Cancer Institute (NCI) grants to the Gynecologic Oncology Group (GOG), NRG Oncology and the NRG Network Operations Center and in part by the National Institutes of Health/NCI. Roche/Genentech supported the NCI cooperative research and development agreement enabling this trial.
Coleman RL, Spiritos NM, Enserro D, et al. Secondary Surgical Cytoreduction for Recurrent Ovarian Cancer. N Engl J Med 2019; 381(20):1929-1939. DOI: 10.1056/NEJMoa1902626.