Recurrent Ovarian Cancer Paradigm Continues to Evolve

Madeleine B. Courtney Brooks, MD, MPH

Chemotherapy is the foundation of treatment for patients with recurrent ovarian cancer, but according to Madeleine B. Courtney Brooks, MD, MPH, conversations regarding the potential for secondary debulking and use of bevacizumab (Avastin) may also be warranted.

“Chemotherapy is the mainstay of treatment for most women with recurrent ovarian cancer,” said Brooks. “It is the tool we use most commonly to try to provide patients with as much time as we can while ensuring that we maintain quality of life.”

However, data from the phase III AGO DESKTOP III/ENGOT ov20 study indicate that select patients may benefit from a combined surgical and chemical intervention. Results demonstrated that select patients who underwent secondary debulking had a prolonged progression-free survival (PFS) compared with those who received chemotherapy alone (HR, 0.66; 95% CI, 0.52-0.83; P <.001).

Regarding bevacizumab, the angiogenesis inhibitor has shown an additive PFS benefit of approximately 3 to 4 months in both the platinum-sensitive and -resistant settings. However, the agent’s role continues to be explored in combination with chemotherapy as well as in conjunction with PARP inhibitors and immunotherapy.

Additionally, the PARP inhibitors niraparib (Zejula), rucaparib (Rubraca), and olaparib (Lynparza) all have approved indications in the maintenance setting for those with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy.

In an interview during the 2019 OncLive^® State of the Science Summit™ on Ovarian Cancer, Brooks, a gynecologic oncologist at the University of Pittsburgh Medical Center, shed light on the current treatment paradigm of recurrent ovarian cancer.

OncLive^®: What is the role of chemotherapy in recurrent ovarian cancer?

Brooks: In general, chemotherapy is palliative in the recurrent setting. We like to think of recurrent ovarian cancer as more of a chronic disease in which we’re working to extend people's lives as much as possible and minimize adverse events and complications.

Could you shed light on the role of secondary debulking? How have the results of the DESKTOP III trial impacted its role in the recurrent setting?

Women who have had a relatively long disease-free interval of at least 1 year after completing primary therapy have platinum-sensitive disease. We would consider surgical intervention in these women.

The goal of the DESKTOP trials was to try and identify a population of women with platinum-sensitive recurrent ovarian cancer who would benefit from secondary debulking. The first two studies retrospectively identified factors that would help identify this group of women, including optimal resection at the time of their initial surgery, no ascites at the time of recurrence, and a good ECOG performance status. DESKTOP III took women with platinum-sensitive disease who fell into that category and randomized them to receive chemotherapy or surgery followed by chemotherapy. Investigators found that surgery plus chemotherapy resulted in about a 5-month improvement in PFS. We’re still awaiting more mature overall survival (OS) data. However, it was an encouraging finding.

What are the next steps that will be taken with this research?

The GOG-213 trial is the second phase III trial examining a similar question [but with bevacizumab and carboplatin/paclitaxel]. It was presented in abstract form, but it gave us slightly different information. We're still awaiting the full publication so we can get more details on which groups of patients may potentially benefit from secondary debulking.

Where is bevacizumab best used in this space?

We know bevacizumab plays a role in the treatment of [patients with] recurrent ovarian cancer, but it’s a question we ask ourselves all the time. There are data looking at bevacizumab upfront in women with platinum-sensitive disease, after surgery, in patients who are not great candidates for secondary debulking initially in conjunction with platinum-based chemotherapy, and as maintenance therapy. We have seen mixed results. In general, we see about a 3- to 4-month improvement in PFS with the addition of bevacizumab. The impact on OS is a little less clear.

We have gotten different results from different trials. We have data from the AURELIA trial in the platinum-resistant setting, which showed that the use of bevacizumab in combination with a cytotoxic agent resulted in a 3- and 4-month improvement in PFS. I find those data very compelling because the trial was done in a group of patients for whom we don't have other great treatment options available. For someone with platinum-resistant disease, a 3- to 4-month improvement in PFS is clinically significant. According to the AURELIA data, bevacizumab seems to be relatively well tolerated as well.

What are some key challenges in this setting?

In the grand scheme of things, the overall response rates are still relatively low. Women who have platinum-sensitive disease and a long platinum-free interval have, at best, a 20% to 50% response rate. It's better than what we see in platinum-resistant disease, but we would like it to be better. Certainly, women with platinum-resistant ovarian cancer have fairly low response rates across the board, in the 10% to 15% range, whether with cytotoxic chemotherapy alone, chemotherapy plus antiangiogenic agents, or targeted therapies. We're always looking for a better solution.

Where do you see future research heading?

A lot of what we're looking at now is the use of targeted agents in combination with chemotherapy. Immunotherapy in combination with other targeted agents is also a topic of interest.

PARP inhibitors in combination with antiangiogenic agents or with immunotherapy are exciting. The question of [administering] a PARP inhibitor after another PARP inhibitor, and whether there is a role for second-line PARP therapy is something I'm looking forward to hearing more about as well.

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.