Second Surgery Extends Progression-Free Survival in Recurrent Ovarian Cancer With Positive AGO Score

Andreas Du Bois, MD

A second cytoreductive surgery followed by platinum-based chemotherapy extended progression-free survival (PFS) compared with platinum-based chemotherapy alone in patients with relapsed ovarian cancer and a positive Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) score. Results from the DESKTOP III study also confirmed a clinically meaningful increase in the median time to start of first subsequent therapy (TFST) in this patient population, announced Andreas Du Bois, MD, at the 2017 meeting of the American Society of Clinical Oncology.¹

The improvements realized in the surgical arm were observed exclusively in patients with complete resection, and are “at least comparable with all so far published phase III trials in second-line therapy for platinum-sensitive recurrent ovarian cancer,” said Du Bois. With an advantage of 5.6 months in median PFS and 7.1 months in median TFST with a second surgery, “it is the most positive trial ever reported in this population. I am talking about therapy trials, not the maintenance trials.”

Importantly, there was no trade-off observed in increased mortality or excessive toxicity with the improvement in the aforementioned endpoints, said DuBois, professor of Gynecologic Oncology, Kliniken Essen Mitte in Essen, Germany.

Until now, the role of secondary cytoreductive surgery for recurrent ovarian cancer was not defined by high-level evidence, although retrospective and non-randomized series had suggested a potential benefit in selected patient cohorts. The AGO score was developed in an effort to predict operability in patients with a first recurrence of ovarian cancer. A positive AGO score assumes resectability with the presence of 3 factors: good performance status (ECOG 0), complete resection at first surgery, and ascites ≤500 mL. The DESKTOP II study confirmed the predictive value of the AGO score; it was able to predict with 95% probability a complete resection in more than two thirds of patients.²

DESKTOP III was designed to evaluate in a prospectively randomized multicenter setting whether cytoreductive surgery followed by platinum-based combination chemotherapy can improve overall survival (OS) compared with platinum-based combination chemotherapy alone in AGO score-positive patients with platinum-sensitive recurrent ovarian cancer.

The study enrolled 407 patients with ovarian cancer, a positive AGO score, and first relapse after at least 6 months of a platinum-free interval. Eighty centers in 12 countries participated. Chemotherapy regimens were selected according to each institution’s standard. An interim analysis was planned after 122 OS events with a significance level set toP= .0052 for early unblinding.

The median platinum-free interval was 18.7 months in the no-surgery arm and 21.1 months in the surgical arm (P= .39), and the platinum-free interval >12 months in three fourths of patients in both arms (P= .80). Some 3.9% of patients underwent surgery despite randomization to the no-surgery arm and 5.9% randomized to surgery did not undergo an operation. Ninety-one percent of patients in the no-surgery arm received platinum-containing therapy, compared with 88.7% of patients in the surgical arm. The macroscopic complete resection rate in the surgical arm was 72.5%.

The pooled 2-year survival rate was 83%, which was much higher than the anticipated 55% to 66% rate, noted Du Bois. Because the interim analysis did not achieve the predefined significance level, the independent data safety monitoring committee recommended that follow-up continue until 244 planned OS events occur for the final OS analysis, which will require approximately 2 more years, he said.

The median PFS in the intent-to-treat population was 19.6 months in the surgical arm compared with 14.0 months in the no-surgery arm (HR, 0.66;P< .001). In the patients who experienced complete resection, the median PFS improved to 21.2 months (HR, 0.56 vs no-surgery arm;P< .0001).

The median TFST (time to third-line therapy) was 21.0 months in the surgical arm versus 13.9 months in the no-surgery arm (HR, 0.61;P< .001).

At 90 days, there was 1 death in each arm. Six-month mortality was 2.46% in the surgical arm arm and 0.49% in the no-surgery arm. Among the grade 3/4 adverse events that occurred within 60 days, only leukopenia/neutropenia was more frequent in the no-surgery arm (5% vs 1%;P= .02).

The benefit exclusive to patients with complete resection underscores the importance of &ldquo;selecting both the right institution with capability to achieve a complete resection and the right patients,&rdquo; Du Bois said. &ldquo;Hopefully, further follow-up will show that this benefit translates into overall survival.&rdquo;

References:

1. Du Bois A, Vergote I, Ferron G, et al. Randomized controlled phase III study evaluating the impact of secondary cytoreductive surgery in recurrent ovarian cancer: AGO DESKTOP III/ENGOT ov20.J Clin Oncol.2017;35(suppl;abstr 5501).
2. Harter P, Sehouli J, Reuss A, et al. Prospective validation study of a predictive score for operability of recurrent ovarian cancer: the Multicenter Intergroup Study DESKTOP II. A project of the AGO Kommission OVAR, AGO Study Group, NOGGO, AGO-Austria, and MITO.Int J Gynecol Cancer.2011;21(2):289-295.