Cytoreductive Surgery Plus Chemo Yields Longer OS vs Chemo Alone in Recurrent Ovarian Cancer

Treatment with cytoreductive surgery and chemotherapy improved overall survival (OS) compared with chemotherapy alone in a population of patients with recurrent ovarian cancer, according to data from the DESKTOP III trial (NCT01166737).¹

Findings from the study indicated that patients who underwent surgery achieved a median OS of 53.7 months (95% CI, 46.8-61.6) compared with 46.0 months (95% CI, 39.5-52.6) among those who did not receive surgery (HR, 0.75; 95% CI, 0.59-0.96; P = .02). Moreover, those who received a complete resection achieved the best outcomes with a median OS of 61.9 months (95% CI, 55.3-78.9) compared with 27.7 months (95% CI, 23.5-38.7) among patients who did not receive a complete resection. The benefit from surgery was observed across all subgroup analyses.

“Cytoreductive surgery in addition to platinum-based chemotherapy in patients with relapsed ovarian cancer resulted in a benefit with respect to overall survival. Appropriate selection of patients and trial centers was crucial for the success of this trial, and the importance of these selections is reflected in both the high efficacy and low morbidity in the trial. The observed incidence of perioperative complications was lower than the incidence that has been reported among patients with primary ovarian cancer,” the investigators wrote.

The role of surgery within this patient population has not been well defined, according to the investigators. Notably, the DESKTOP I trial was able to confirm the benefit of complete resection within this patient population, which appeared to be greater than the impact of upfront cytoreductive surgery.² As the long-term benefit appeared to only be associated with complete resection, investigators concluded that a predictive score would be necessary in order to better identify patients who were likely to achieve a complete resection. This was done to select patients for a prospective trial utilizing cytoreductive surgery.

Patients were required to have been diagnosed with epithelial ovarian cancer and have relapsed disease identified within at least 6 months following their last course of initial platinum-based chemotherapy. Moreover, patients were required to have a positive Arbeitsgemeinschaft Gynäkologische Onkologie score. However, an elevated cancer antigen 125 level excluded patients from the study.

Those who were eligible for the trial were randomized 1:1 to either undergo surgery followed by physician’s choice of platinum-based chemotherapy or chemotherapy alone. Although the protocol suggested the use of a combination regimen, only 1 agent was allowed. Patients were stratified based on center and platinum-free interval.

The primary end point was OS, with key secondary end points including quality of life at baseline, 6 months, and 9 months; progression-free survival (PFS); complete resection as a prognostic factor; and complications up to 60 days following surgery.

Investigators enrolled a total of 407 patients on the study, 206 of whom were stratified to the surgery group and 201 who received chemotherapy alone. Baseline characteristics were well balanced, with the majority of patients having previously received platinum-based chemotherapy at their first diagnosis. Additionally, 75% of patients in both groups had a platinum-free interval lasting 12 months.

Among patients in the surgery group, 93.2% underwent the procedure. The remaining patients did not undergo surgery due to several factors, such as intercurrent illness following randomization, findings indicating that resection was not possible, loss to follow-up, and erroneous communication. A total of 75.5% of patients achieved macroscopic complete resection. No deaths were reported within 30 days of undergoing surgery. Additionally, 3.7% of patients received reoperation.

The study had a median follow-up of 69.8 months. Additional findings from the trial indicated that patients in the surgery arm had a median PFS of 18.4 months (95% CI, 15.7-20.8) vs 14.0 months (95% CI, 12.7-15.4) in the chemotherapy only arm (HR, 0.66; 95% CI, 0.54-0.82).

Notable differences were not observed in global health status, quality of life, or function subscale at baseline were noted in the quality of life analysis at 6 months or 12 months. Investigators reported that model-based estimates of changes from baseline between the 2 groups at 6 months were 9.0 on the insomnia scale and 12.2 points on the constipation scale; both appeared to favor the no surgery group. However, at 6 months, 11% of patients in the chemotherapy only group were still receiving treatment compared with 38% of patients in the surgery group.

References

1. Harter P, Sehouli J, Vergote I, et al. Randomized trial of cytoreductive surgery for relapsed ovarian cancer. N Engl J Med. 2021;385:2123-2131. doi:10.1056/NEJMoa2103294
2. Du Bois A, Reuss A, Pujade-Lauraine E, et al. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials. Published online March 3, 2009. doi:10.1002/cncr.24149