Maintenance Therapy for Advanced Ovarian Cancer

Ramez N. Eskander, MD: Maintenance therapy is an important component of the treatment of patients with advanced ovarian cancer. This has transformed our management of advanced-stage ovarian cancer in the last 3 years. What we’ve discovered is that we have several opportunities for maintenance treatment during therapy. I’ll start in the frontline setting.

Again, based on the results of both PRIMA as well as the PAOLA-1 trial, we now have opportunities for maintenance PARP inhibition in the frontline setting for an all-comer population, and that’s niraparib. That’s based on an improvement in the median progression-free survival, with the goal being to extend the interval of time in which the patient is in remission, which will potentially facilitate alternate treatment options down the line.

In the PAOLA-1 study, the combination of bevacizumab plus olaparib was compared against bevacizumab plus placebo. And in that patient population, the approval was in those with a homologous recombination deficiency [HRD] who, again, appeared to have a significant benefit over bevacizumab plus placebo with the addition of a maintenance olaparib regimen. Both of these studies followed the approval of maintenance single-agent olaparib in 2018, and that was based on the SOLO-1 trial specifically in the BRCA-mutated germline or somatic patient population. So we went from having a maintenance strategy with olaparib, specifically in the BRCA-mutated population, to now having maintenance opportunities with niraparib in the all-comer population, or olaparib plus bevacizumab in patients who are homologous recombination deficient, including those with a BRCA mutation.

And briefly we touch on the fact that bevacizumab was the initial maintenance strategy that was approved for us quite a while back as an antiangiogenic agent. Some patients may have been on bevacizumab with chemotherapy and continued on maintenance bevacizumab. Now you get into the discussion of, how can we layer these maintenance approaches, and is there relevance to sequentially applying these medications versus using them in combination? Those data have yet to be developed.

In the platinum-sensitive recurrent setting, meaning patients who have responded to their most recent penultimate platinum regimen, maintenance strategies again include single-agent bevacizumab, as an antiangiogenic agent, or maintenance PARP inhibition, again with 3 options: niraparib, olaparib, and rucaparib. Both options are based on a meaningful improvement in the median progression-free survival with incorporation of maintenance treatment.

I like to think that maintenance has become incorporated into the management of our patients. We now have maintenance opportunities in the frontline setting, and we have maintenance opportunities in the platinum-sensitive recurrent setting. It’s our obligation to try to sit with our patients and figure out which strategy and which drug regimen may be the most appropriate for them based on their disease status and their tumor testing. Because, again, all of this hinges on the information that we get from genetic testing, germline assessments of BRCA1 and BRCA2, genomic assessments of the tumor looking at this genomic signature of homologous recombination deficiency, of which one component is loss of heterozygosity, or LOH, and other aberrations that we can identify in gene sequencing, such as RAD51C or RAD51D mutations, not all of which always equate to a high LOH score.

I do anticipate that maintenance therapy is going to become ubiquitous in the ovarian cancer space. I think there was, very early, an aggressive adoption of olaparib in the patients with BRCA mutations. Many of us are excited that now has expanded beyond BRCA to include HRD and all-comers as potential options with the combination regimens or with single-agent niraparib. And certainly in the platinum-sensitive recurrent setting, where our goal is to truly extend that chemotherapy-free interval, incorporation of a maintenance PARP inhibitor is also an attractive option. I would argue that maintenance therapy in ovarian cancer is here to stay, both in the frontline setting and in the platinum-sensitive recurrent setting.

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