Secondary Surgical Cytoreduction for Recurrent Ovarian Cancer

초록

The National Comprehensive Cancer Network recommends secondary cytoreduction for ovarian cancer patients with recurrent disease who have received no treatment for a period of 6 months following a complete response from prior chemotherapy. Retrospective reviews and meta-analyses have shown the most benefit from this operation in those with platinum-sensitive disease and those with little or no postoperative residual disease. This open-label, phase 3 randomized clinical trial assessed whether secondary cytoreduction would increase overall survival among patients with platinum-sensitive, recurrent ovarian cancer. This study also evaluated whether bevacizumab added to carboplatin and paclitaxel chemotherapy followed by maintenance bevacizumab improves overall survival. Patients were enrolled into the surgical or chemotherapy portion of the trial if they met the criteria to be considered for secondary cytoreduction at enrollment. Patients ineligible for the surgery component were enrolled in the chemotherapy portion only. Subjects enrolled in the surgery component required measurable disease by RECIST 1.0, platinum-sensitive epithelial ovarian cancer deemed amenable to gross resection. Eligibility required a complete clinical response following at least 3 cycles of previous platinum-based chemotherapy. Subjects amenable to surgery also underwent randomization in a 1:1 ratio to 6 cycles of either paclitaxel and carboplatin or paclitaxel, carboplatin, and bevacizumab. Subjects assigned to surgery underwent the procedure within 4 weeks of registration, and chemotherapy was administered within 6 weeks of registration or 6 weeks postoperatively. Baseline imaging was obtained via computed tomography or magnetic resonance imaging and again after cycles 3 and 6, every 3 months for 2 years, and every 6months thereafter. Overall survival was measured from randomization to death from any cause on an intent-to-treat basis. Four hundred eighty-five subjects were randomly assigned to secondary surgical cytoreduction followed by platinum-based chemotherapy (n = 240) or chemotherapy alone (n = 245) between December 6, 2007, and June 9, 2017. Of the 225 subjects who underwent surgery, 67% achieved complete gross resection. The majority of subjects (84%) received concomitant and maintenance bevacizumab. The percentage of subjects alive at 3 years postinitiation was 67% (95% CI, 60-74) and 74% (95% CI, 68-81) in the surgery and nonsurgery groups, respectively. The adjusted hazard ratio for death (surgery vs no surgery) was 1.29 (95% CI, 0.97-1.72; P = 0.08), corresponding to a median overall survival of 50.6 and 64.7 months, respectively. Adjusted hazard ratio for disease progression or death (surgery vs no surgery) was 0.82 (95% CI, 0.66-1.01), corresponding to a median progression-free survival of 18.9 and 16.2 months, respectively. The results of this study show that among women with platinum-sensitive, recurrent epithelial ovarian cancer, secondary cytoreduction followed by chemotherapy did not result in a longer overall survival than chemotherapy alone. The hazard ratio for disease progression or death does not indicate surgery plus chemotherapy as a superior intervention to chemotherapy alone.