Secondary Surgical Cytoreduction for Recurrent Ovarian Cancer

Abstract

Background: Secondary surgical cytoreduction in women with platinum-sensitive, recurrent epithelial ovarian, primary peritoneal, or fallopian-tube ("ovarian") cancer is widely practiced but has not been evaluated in phase 3 investigation.

Methods: We randomly assigned patients with recurrent ovarian cancer who had received one previous therapy, had an interval during which no platinum-based chemotherapy was used (platinum-free interval) of 6 months or more, and had investigator-determined resectable disease (to no macroscopic residual 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 primary end point was overall survival.

Results: A total of 485 patients underwent randomization, 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 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 overall survival of 50.6 months and 64.7 months, respectively. Adjustment for platinum-free interval and chemotherapy choice did not alter the effect. The hazard ratio for disease progression or death (surgery vs. no surgery) was 0.82 (95% CI, 0.66 to 1.01; median progression-free survival, 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.

Conclusions: 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. (Funded by the National Cancer Institute and others; GOG-0213 ClinicalTrials.gov number, NCT00565851.).

Figure 1.. Randomization and Follow-up.

Patients who were included in the intention-to-treat analysis were evaluated for overall survival and progression-free survival.

Figure 2.. Quality of Life.

The plot lines represent the patient-reported scores on the Trial Outcome Index of the Functional Assessment of Cancer Therapy–Ovary (FACT-O TOI). Scores range from 0 to 100, with higher scores indicating a better quality of life. The estimates of least-squares mean scores were obtained from a fitted mixed model that was adjusted for pre-treatment score (baseline score), chemotherapy received, the country in which the treatment was given, the interval during which no platinum-based chemotherapy was used (platinum-free interval) before recurrence (6 to 12 months vs. >2 months), and the patient’s age at enrollment. Surgery was associated with significantly lower postoperative FACT-O TOI scores. The scores were similar in the two groups at 6 weeks after treatment and at every subsequent assessment.

Figure 3.. Overall Survival and Progression-free Survival.

Shown are overall survival (primary outcome; Panel A) and progression-free survival (Panel B) among patients randomly assigned to surgical cytoreduction and chemotherapy (cytoreductive-surgery group) or chemotherapy alone (no-surgery group).

Figure 4.. Subgroup Analysis for Overall Survival.

Shown are hazard ratios for the effect of cytoreductive surgery on overall survival according to stratification variables (chemotherapy regimen and platinum-free interval) and patient characteristics. The results of statistical testing of the interaction between treatment and subgroup factors suggest reasonable consistency of the treatment effect within randomization strata as well as demographic and prognostic subgroups. Ethnic group was reported by the patients.