Advanced Ovarian Cancer Treatment Strategies

Ramez N. Eskander, MD: Women who present with advanced-stage or metastatic ovarian cancer, which is the vast majority—over 75% will present with stage III or IV disease—are usually treated with neoadjuvant chemotherapy. The reason that’s the case is because the intent is to help control the disease burden. Then, when we do explore them surgically at the time of an interval surgical evaluation, we’re able to remove all of the visible tumor. What we don’t want is perform a surgery where we leave significant gross tumor behind, because we believe that’s not therapeutically beneficial for the patient.

Systemic chemotherapy in the frontline setting for patients with stage IV disease is usually predicated on a backbone of combination carboplatin and paclitaxel. This regimen is now most commonly given in a Q3 [every 3]-week regimen. It can be given with the paclitaxel administered weekly, based on the Japanese GOG study, and some providers are still using intraperitoneal chemotherapy. Although, after Gynecologic Oncology Group protocol 252 was presented and published, that has fallen away to some degree.

One of the other treatment strategies or approaches is the incorporation of antiangiogenic bevacizumab. Based on both GOG-0218 and ICON7, we know that bevacizumab in the front line leads to a meaningful improvement in progression-free survival. There may be a signal, based on the GOG-0218 data as well as ICON7, looking at the impact of bevacizumab plus chemotherapy in the front line for those stage IV or high-risk patients, and they may benefit the most. In GOG-0218, there was about a 10-month overall survival difference between the bevacizumab throughout arm and the controlled placebo arm.

So for patients with stage IV disease, it’s traditionally chemotherapy, or chemotherapy plus bevacizumab with maintenance bevacizumab. Most recently, we’ve also had exciting data, both based on a presentation at ESMO, or the European Society for Medical Oncology, and subsequent publications in The New England Journal of Medicine, for maintenance niraparib in the frontline setting, based on the PRIMA trial, or a maintenance frontline combination of olaparib plus bevacizumab, based on the PAOLA-1 clinical trial. Both of those studies met their primary end points, showing a significant improvement in progression-free survival. Both of those have resulted in US FDA approval of these maintenance strategies.

In someone who is newly diagnosed at this point with stage IV disease, there are several options. The carboplatin and paclitaxel chemotherapy backbone will be integral, but then you layer onto that the opportunity for bevacizumab with maintenance bevacizumab alone; maintenance bevacizumab plus olaparib, if that patient is homologous recombination deficient, based on the FDA label; or maintenance niraparib as a single agent for all-comers, based on the US FDA label for the PRIMA trial. So we’ve now, in a short period, had several opportunities introduced to us in the maintenance frontline setting for patients with stage IV ovarian cancer.

When we talk about ovarian cancer recurrence, one of the early decision trees is figuring out if this is a platinum-sensitive or a platinum-resistant disease recurrence. That’s driven by the interval of time between completion of chemotherapy and recurrence of disease. Some of us are trying to avoid that dichotomous choice, and we talked about a platinum-free interval as a continuous variable. Nonetheless, if we talk about platinum-sensitive disease recurrence, which was reflected in the case discussed earlier, we are thinking about patients who’ve responded to their initial treatment, had a treatment-free interval of at least 6 months. In those patients, again, a platinum-based combination regimen is the standard of care. But what we’ve also seen, based on prior studies such as ARIEL3, SOLO-2, and Study 19, as well as NOVA, maintenance PARP inhibition in the platinum-sensitive recurrent space can result in a meaningful improvement in progression-free survival, particularly with a notable signal in the homologous recombination deficient patient populations.

And so, we have FDA approvals for 3 PARPs in that setting, specifically, olaparib, rucaparib, and niraparib as maintenance strategies in the platinum-sensitive recurrent setting for those patients who have a complete or partial response to their most recent platinum doublet combination. We also need to remember that bevacizumab also has an approval in the platinum-sensitive recurrent setting as a maintenance strategy. Again, that’s based on efficacy data from GOG-0213. So we have options. We have maintenance PARP or maintenance antiangiogenic bevacizumab in this setting based on several factors, including how the patients responded to initial treatment and their performance status, and then we have options for subsequent therapy.

Transcript edited for clarity.

Case: A 71-Year Old Woman With High-Risk Ovarian Cancer

Initial presentation

• A 71-year old woman presented to her PCP for a routine annual checkup, she complains of increasing fatigue
• PMH:
  • Hypertension, controlled on a thiazide
  • 2017 diagnosed with stage IV ovarian cancer; BRCAwt; underwent TAH/BSO, lymph node dissection, with suboptimal debulking; treated with paclitaxel/carboplatin/bevacizumab followed by maintenance bevacizumab; achieved CR

Currently

• CA-125, 456 U/mL
• Chest/abdomen/pelvis CT with contrast shows a suspicious lung lesion
  • Lung biopsy confirmed recurrent epithelial ovarian cancer
• Molecular testing showed HRD+, LOH high
• ECOG: 0

Treatment and Follow-Up

• She was started referred to an oncologist and started on carboplatin/doxorubicin, treatment was well tolerated for 4 cycles; CA-125 35 U/mL;
  • Rucaparib 300 mg BID maintenance was initiated
• At 2 months follow-up
  • CA-125 was undetectable
  • Chest/abdomen/pelvis CT showed no gross masses or nodes
  • Pelvic exam was unremarkable