Recent Data Muddle Role of Secondary Surgery in Recurrent Ovarian Cancer

Sarah Crafton, MD

Despite being utilized in clinical practice, the optimal role of secondary surgical cytoreduction is not widely understood in recurrent ovarian cancer, said Sarah Crafton, MD.

"Ultimately, surgical cytoreduction for recurrence may have a role for subpopulations of our patients," said Crafton. "At the time of recurrence, all patients with ovarian cancer should have a gynecologic-oncology consultation, even if just to reaffirm that they are not surgical candidates. It is an important conversation to have because surgery may influence survival after recurrent disease."

However, in November 2019, final results of the randomized phase III GOG-213 trial were published in the New England Journal of Medicine.

The data failed to demonstrate an overall survival (OS) benefit with secondary surgical cytoreduction followed by chemotherapy compared with chemotherapy alone in women with platinum-sensitive, recurrent ovarian cancer. At a median follow-up of 48.1 months, the median OS was 50.6 months versus 64.7 months, respectively (HR, 1.29; 95% CI, 0.97-1.72; P = .08).¹

Conversely, interim results for the randomized phase III AGO DESKTOP III/ENGOT ov20 (DESKTOP III) trial, which is awaiting final OS data, showed a clinically meaningful PFS and time to start of first subsequent therapy (TFST) improvement with surgery over second-line chemotherapy in patients with first-relapse, AGO-positive ovarian cancer who had a platinum-free interval of ≥6 months. The median PFS was 19.6 months versus 14.0 months (HR, 0.66; 95% CI, 0.52-0.83; P <.001), and median TFST was 21.0 months versus 13.9 months (HR, 0.61; 95% CI, 0.48-0.77; P <.001), in favor of surgery.²

In an interview during the 2019 OncLive^® State of the Science Summit™ on Ovarian Cancer, Crafton, a gynecologic oncologist at Allegheny Health Network, discussed the role of secondary surgical cytoreduction in recurrent ovarian cancer.

OncLive: What factors must be taken into consideration for secondary surgical cytoreduction?

Crafton: There are 2 large, randomized, controlled trials that demonstrate the role of surgical cytoreduction in recurrent ovarian cancer. They were both presented at ASCO Annual Meetings within the last few years. Unfortunately, the trials have conflicting results.

The large European trial demonstrated that there are patients who have a good performance status, low-volume ascites, and had an optimal initial primary cytoreduction may be good candidates for secondary surgery. In addition, that trial demonstrated a PFS benefit.

However, the GOG-213 trial [that was recently published in The New England Journal of Medicine] showed no advantage of PFS or OS in patients who had surgery and chemotherapy versus chemotherapy alone.

What questions remain regarding this procedure?

Assessing the role of secondary cytoreduction has to be a personalized choice. It is not only based on objective data from studies, but also patient preference.

Typically, these patients have undergone a primary cytoreductive surgery that may either influence them positively or negatively about aspiring to a second surgery. It has to be a completely personalized conversation.

The DESKTOP III data show that we at least have some criteria we can use to direct our counseling and selection.

Do you have advice for other physicians trying to converse with patients about whether to go to surgery or receive systemic therapy?

The best advice is to base the decision on the energy your patient brings. Some patients are excited about a second surgery as a motivation factor. There is also an opportunity to palliate a patient’s symptoms, especially if they have high disease burden. That would be influential in counseling.

You can get a good grasp of what your patients are favoring, and there is no strong data to support one option over the other. Respecting the patient's decision-making process is the most important.

If a patient does undergo systemic therapy, what options are available? What factors should be considered when making a treatment decision?

When it comes to recurrent ovarian cancer, our primary decision-making key is their platinum—sensitive status, or the period of time between their last platinum agent to the time of recurrence. That single-handedly makes the first decision for us.

There is a wide variety of platinum combination therapies with or without targeted therapies that can be utilized. Without using cross-trial comparison, the combinations have all demonstrated efficacy in those platinum-sensitive patients. The National Comprehensive Cancer Network publishes a summary of agents for platinum-sensitive and platinum-resistant disease.

At first glance, these lists look very long. Unfortunately, there is a lot of overlap between the agents, so the number of them is not as many as it seems.

Tailoring those lengthy lists to a patient’s prior toxicities, disease-related symptoms, prior [response to platinum-based therapy], and functional status is important to choose the most appropriate agent.

What patients may be good candidates to receive antiangiogenic agents?

We can all agree that the role of bevacizumab (Avastin) has influenced ovarian cancer in the up front and recurrent settings. In the recurrent setting, surgery has a smaller role than in up front treatment and we have less options, especially as patients progress through lines of therapy. Thankfully, we have data from trials such as AURELIA, which shows that adding an antiangiogenic agent to chemotherapy improves response rates and PFS.

What questions do we still need to answer in terms of systemic therapy?

We do not have the optimal genetic testing information that we need. Everyone agrees that it is important to obtain both germline and somatic BRCA mutation information in the frontline setting. However, all other tumor testing, panels, timing, and repeat testing are all to be determined, but those pieces of information influence what our treatment options are.

References

1. Coleman RL, Spirtos NM, Enserro D, et al. Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med. 2019;381(20):1929-1939. doi: 10.1056/NEJMoa1902626.
2. 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 15;abstr 5501). doi: 10.1200/JCO.2017.35.15_suppl.5501.