Jalid Sehouli, MD
Patients with relapsed ovarian cancer and a positive Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) score experienced prolonged progression-free survival (PFS) after undergoing a second cytoreductive surgery followed by platinum-based chemotherapy.
In results from the DESKTOP III study presented at the 2017 international meeting of the European Society of Gynaecological Oncology (ESGO 20), median PFS in the intent-to-treat population was 19.6 months in the surgery arm compared with 14.0 months in the no-surgery arm (hazard ratio [HR], 0.66; 95% CI, 0.52-0.83; P
“Although retrospective and non-randomized series had suggested a potential benefit in selected patient cohorts, survival following salvage surgery for recurrent ovarian cancer had not been defined by randomized studies,” said Jalid Sehouli, MD, Charité Universitätsmedizin Berlin.
The AGO score was developed to predict surgical success in patients with a first recurrence of ovarian cancer. A positive AGO score is based on the presence of 3 factors: good performance status (ECOG 0), complete resection at first surgery, and ascites ≤500 mL, and suggests the likelihood of achieving complete resection, according to Sehouli. In DESKTOP II, a positive AGO score predicted a complete resection in more than two-thirds of patients with 95% probability.
While DESKTOP II confirmed the predictive value of AGO, DESKTOP III was designed to evaluate overall survival (OS) in patients with a positive AGO score treated with chemotherapy plus a second surgery as the primary endpoint. Secondary endpoints included PFS, resection rate, and treatment burden.
The prospective, randomized multicenter DESKTOP III compared OS for patients who underwent cytoreductive surgery followed by platinum-based combination chemotherapy (n = 204) with OS for those assigned to chemotherapy alone (n = 203). All patients had platinum-sensitive recurrent ovarian cancer following cytoreductive surgery and were AGO score-positive.
Patient characteristics were balanced regarding age, FIGO stage IIIB-IV, and prior treatment history. Histology was G2/3 serous in 83.8% versus 77.3% in the surgery versus no-surgery arms (P
= .11), and the median platinum-free interval was 21.1 versus 18.7 months, respectively (P
= .39). Post randomization, 88.7% of patients in the surgery arm and 91.1% of patients in the no-surgery arm received platinum-containing therapy.
In all, 5.9% in the surgery arm were non-compliant with randomization versus 3.9% in the no-surgery arm. Twelve patients randomly assigned to surgery elected against the procedure and 8 patients assigned to no-surgery underwent resection.
The median duration of surgery was 220 minutes (range, 150-300 minutes). The median blood loss was 250 mL (range, 50-500 mLs), and 20.3% of patients required red blood cell (RBC) transfusion.
Investigators observed fever 4.8% of patients, and 19.0% of patients received antibiotic treatment, mainly for urinary tract infection. Perioperative thrombosis occurred in 1.1% of patients, and the re-laparotomy rate was 3.2%.
The macroscopic complete resection rate was 72.5% in the patients undergoing salvage surgery.
Where complete resection was achieved, the median PFS improved to 21.2 months compared with the no-surgery patients (HR, 0.56; P
“A clear benefit with surgery was exclusively seen in patients with complete resection indicating the importance of to patients with complete resection underscores the importance of selecting both the right institution with capability to achieve a complete resection and the right patients—in this case, selection by AGO score,” Sehouli said.
Investigators noted a 7.1-month difference in the median time to third-line therapy (TFST) favoring surgery. Median TFST was 21.0 months in patients undergoing surgery versus 13.9 months in the no-surgery arm (HR, 0.61; 95% CI, 0.48-0.77; P
One patient (0.49%) in the surgery arm died within 90 days post-study entry compared with 1 patient (0.49%) each within 60 and 90 days post-study entry in the no surgery arm. The 6-month mortality rate favored surgery, 0.49% 2.46%.
The most commonly reported grade 3/4 adverse events (AEs) observed within 60 days in both arms were fatigue, GI-fistula, neuropathy, and thrombosis/embolism, which occurred in less than 1% of patients. Grade 3/4 leukopenia/neutropenia occurred more frequently in the no-surgery arm at 5% versus 1% with surgery (P
“Second cytoreductive surgery resulted in a PFS and TFST advantage of 5.6 and 7.1 months,” summarized Sehouli. “We anticipate further follow-up will show that this benefit translates into overall survival. Overall survival results will be presented in 2019.”
Sehouli J, Vergote I, Ferron G, et al. Randomized controlled phase III study to evaluate secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer - AGO DESKTOP III/ENGOT OV20. Presented at: the European Gynacological Oncology Congress 2017; November 4-7, 2017; Vienna, Austria; EP07.