Secondary Cytoreductive Surgery Shows Promise in Ovarian Cancer

Jalid Sehouli, MD

While surgery is a mainstay in the primary treatment of recurrent ovarian cancer, the role of secondary cytoreductive surgery has yet to be defined.

In a phase III study of patients with platinum-sensitive recurrent ovarian cancer, the impact of secondary cytoreductive surgery was evaluated. The AGO DESKTOP III/ENGOT ov20 trial randomized patients to second-line chemotherapy alone versus cytoreductive surgery followed by chemotherapy. Enrolled patients had a positive AGO-score, defined as an ECOG performance status of 0, ascites ≤500 ml, and complete resection at initial surgery.

The interim analysis of this trial was presented at the 2017 International Meeting of the European Society of Gynaecological Oncology.

Findings showed that complete resection was achieved in 72.5% of operated patients. The median progression-free survival was 19.6 months in the surgical arm versus 14 months without surgery (HR 0.66; 95% CI, 0.52-0.83, P <.001). The median time to the start of first subsequent therapy was 21 vs 13.9 months, respectively (HR, 0.61; 95%CI, 0.48-0.77, P <.001). Overall survival (OS) data are not yet mature.

Investigators concluded that secondary cytoreductive surgery should be considered an option for patients who have a positive AGO-score until final OS data defines the usage of this treatment option.

OncLive: Please provide an overview of this study.

In an interview during the meeting, lead author Jalid Sehouli, MD, PhD, director of the Clinic Campus Virchow and Campus Benjamin Franklin Charité Center Gynecology, Charité — Universitatsmedizin Berlin, discussed the significance of these findings in the treatment of patients with platinum-sensitive recurrent ovarian cancer.Sehouli: Surgery is the cornerstone in the primary treatment of ovarian cancer followed by subsequent chemotherapy with platinum combinations. But what is the role of salvage surgery in the relapsed setting? We know it is visible, we know there are several data showing that patients who achieve complete resection live longer than patients who do not. But, is it really better than chemotherapy alone? That is the reason that we initiated this trial in patients with platinum-sensitive ovarian cancer using the AGO score, including complete resection at first surgery, and good performance in the platinum-sensitive setting to increase the number of patients where we are able to achieve complete resection. We randomized these patients to surgery followed by chemotherapy, or only chemotherapy.

What were the significant findings?

It was a very tough study because patients like to do surgery, but we were able to do a randomized trial internationally. We have shown that the surgical trial is viable in a multicenter, multinational setting. In our study, we have a high rate of completely-resected patients—around 70%—with a high rate of resection, upper abdominal surgery including splenectomy, and the morbidity was very low. It was much lower than in most published data from multicenter studies. The interim analysis shows a clear significant benefit in progression-free survival. If you compare this with the other trials with medical therapies, this is much better and much longer. We are waiting now for the overall survival data—maybe in 2019, the data will be major enough. What we can say today is that we should offer second surgery in platinum-sensitive ovarian cancer, in combination with chemotherapy as a viable option at trained centers. This is not a "must," this is an option, because relapsed ovarian cancer is a chronic disease.

What do you hope that oncologists take away from these findings?

I wanted to add that the AGO was designed to increase the number of patients where you achieve complete resection, but some of the published data show that even if the AGO score is negative, we are able to achieve complete resection in 50% to 60% of patients. We think it is a variable thing, and we are very proud to present these data for the very first time. I think that it will change the standard of care.I think the story for the patient with first relapse is to look at the condition that they are in. What was the previous treatment? Including surgery or chemotherapy. What is the current tumor pattern? What are the symptoms of the patient? And then they need to try to define the treatment goal. Is it more palliative or is it to prolong survival or the treatment-free interval? If it is difficult to offer surgery based on the infrastructure that you have, then you should refer patient to another center of excellence.

On the other side, I don't like to send patients to any surgery without discussing the alternative medical treatments—and I am a surgeon. It is a part of the multimodel approach for patients with ovarian cancer, and that must be discussed very clear and in detail with your patients.

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. Abstract presented at: 2017 ESGO Congress; November 4-7, 2017; Vienna, Austria.