Predictors of Recurrence in Ovarian Cancer

EP: 1.Case Overview: A 67-Year-Old Woman With Ovarian Cancer

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EP: 2.Predictors of Recurrence in Ovarian Cancer

EP: 3.Molecular Testing in Ovarian Cancer

EP: 4.Options for Maintenance Therapy in Ovarian Cancer

EP: 5.Clinical Trials in Ovarian Cancer Maintenance: PRIMA and NOVA

EP: 6.Platinum Sensitivity vs Resistance and Treatment Selection in Ovarian Cancer

EP: 7.Future Directions in Ovarian Cancer

Chirag Shah, MD, MPH: This is a fairly characteristic patient that we might see in my practice [Swedish Cancer Institute]. The average age of incidence of most nongermline BRCA-mutated ovarian cancers is 61 years of age, so patients often present in the postmenopausal setting with fairly nonspecific symptoms. Thankfully, because of a number of advances that we are going to have the opportunity to discuss today, the survival for ovarian cancer has improved over the last 2 decades, although historically, if we go back to the mid-2000s, we had about a 10-year gap where there was no novel therapeutic agent for women with ovarian cancer.

The biggest issue with women with ovarian cancer is that, although they respond well to frontline chemotherapy as our patient in this hypothetical example did by ending up with a complete remission, there is high relapse rate: 70% to 80% of patients that reach a remission will still have recurrent disease. Unfortunately, a significant proportion will have disease recurrence in less than 6 months, which we use to define what is called the platinum-free interval. If a patient has recurrence in less than 6 months, they are defined as platinum resistant. If their recurrence happens at greater than 6 months, they are defined as platinum sensitive.

The overall prognosis for this patient is improved by the fact that she had a complete surgical cytoreduction. Certainly the longest overall survival we have seen is in patients who were able to be cytoreduced to no gross residual disease, so this is a paradigm shift from a decade ago or longer when an optimal surgical cytoreduction was the goal, where we were just trying to get to less than 1 cm of disease. Suboptimal patients, which are those who have the poorest prognosis, are patients who have greater than 1 cm of disease. First of all, our patient here fell into the best prognostic category in terms of her surgery, ending up with a complete cytoreduction.

We know a priori that patients with stage IV disease tend to do more poorly, and that is where the question of maintenance therapy is in forefront of the management of women with epithelial, ovarian, fallopian tube, and primary peritoneal cancer. Those 3 disease sites, for all intents and purposes, get managed under the same umbrella of ovarian cancer. They are felt to be the same biologically, they are felt to be the same molecularly, and they behave the same clinically.

As I mentioned, the recurrence risk is quite significant, so through rigorous clinical trials and now clinical experience, we have grasped what is occurring in a number of other solid tumors, which is a maintenance therapy. This patient was started on niraparib maintenance, but there are other maintenance options available. The FDA has approved frontline bevacizumab maintenance for patients with epithelial, ovarian, primary peritoneal, and fallopian tube cancers. In addition, with the combination of bevacizumab and olaparib, another PARP inhibitor, or olaparib frontline maintenance, there are various differences to the indications of those particular medications. The FDA approvals for any patient regardless of their status are for niraparib alone as monotherapy in maintenance and bevacizumab as frontline maintenance.

Transcript edited for clarity.

Case: A 67-Year-Old Woman With Ovarian Cancer

Initial Presentation

• A 67-year-old female presented with abdominal discomfort and modest weight loss
• PMH: unremarkable, postmenopausal; no known family history of cancer
• PE: diffuse tenderness to abdominal palpation, abdominal bloating
• ECOG PS 0

Clinical Work-up

• Pelvic exam with transvaginal ultrasound showed a left ovarian mass
• Chest/abdomen/pelvis CT with contrast revealed a left adnexal 5-cm mass, pelvic and inguinal lymph node involvement, no pleural effusion
• Paracentesis (1200cc) cytology confirmed high-grade epithelial ovarian cancer
• Germline molecular testing: HRD+, BRCA1/2-
• CA-125, 360 U/mL
• Diagnosis: Stage 4, high-grade epithelial ovarian cancer

Treatment

• Patient underwent TAH/BSO, lymph node dissection, with optimal debulking; R0
• IP/IV paclitaxel/cisplatin; CR
• Niraparib maintenance was initiated