Treatment of Stage IV Ovarian Cancer
Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor (08/2018)
Individuals diagnosed with stage IV ovarian cancer have disease that has spread outside the abdomen or into the liver. Currently, the standard treatment for stage IV ovarian cancer consists of both surgery and systemic treatment, typically with chemotherapy. Optimal cytoreductive surgery and platinum-based chemotherapy prolong the time to cancer recurrence and improve overall survival. Poly ADP-ribose polymerase (PARP) inhibitors and other newer precision cancer medicines are improving upon the outcomes achieved with platinum based chemotherapy. All patient should discuss the role of clinical trials in the management of stage IV ovarian cancer as many new treatments are being developed.
During cytoreductive surgery, physicians attempt to remove as much of the ovarian cancer as possible. Cytoreductive surgery is beneficial because it reduces the number of cancer cells that ultimately need to be destroyed by chemotherapy and therefore, decreases the likelihood of the cancer developing resistance to chemotherapy. Initial cytoreductive surgery in ovarian cancer is currently considered the standard of care because clinical studies have shown that patients who have had optimal cytoreductive surgery live longer and have a more prolonged time to cancer recurrence than patients who have had suboptimal cytoreductive surgery.1
Following cytoreductive surgery, all patients with stage IV ovarian cancer are offered additional treatment. This is because the majority of stage IV patients will experience recurrence because all cancer cells were not removed by surgery. An effective systemic treatment is needed to eliminate the remaining cancer in order to improve the outcome achieved with surgical removal of the cancer.
The delivery of systemic cancer treatment following surgery is administered to decrease the risk of cancer recurrence following recovery from surgery because treatment prolongs the duration of survival and prevents more recurrences of cancer compared to treatment with alone.1
Current systemic therapy typically consists of a taxane and platinum chemotherapy regimen, however several other chemotherapy and precision cancer medicine drugs are available and others are being developed in clinical trials.
Systemic chemotherapy is most often given after surgery. In some cases, however, it may be given both before and after surgery. Giving systemic therapy before surgery may reduce the amount of cancer, thereby allowing for more complete surgical removal of the cancer. This approach to treatment may be considered for selected patients with advanced disease who do not appear to be candidates for initial surgery.2
Before deciding to receive systemic therapy treatment or to participate in a clinical trial, women should ensure they understand the answer to 3 questions:
- What is my prognosis (risk of cancer recurrence) without adjuvant therapy treatment?
- How will my prognosis be improved with adjuvant treatment?
- What are the risks of treatment?
Strategies to Improve Treatment
The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Because of the poor prognosis with current treatment, all patients with stage IV ovarian cancer should consider participation in a clinical trial. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Active investigation aimed at improving the treatment of ovarian cancer includes the following:
Development of Precision Cancer Medicines: Research is ongoing to develop new medications that specifically target cancer cells in clinical trials. These trials typically require a sample of the cancer or liquid biopsy to be available in order to evaluate for biomarkers. Patients should learn about options to participate in these trials prior to surgery in order to ensure that cancer tissue is obtained correctly. Learn more about development of precision cancer medicines for treatment of ovarian cancer.
PARP Inhibitors: The poly ADP-ribose polymerase (PARP) enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. A new class of precision cancer medicines that target and inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy and are called PARP inhibitors. By blocking this enzyme, DNA inside the cancerous cells is less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of cancer cell growth.
PARP inhibitors have the greatest effect in women with mutations of the BRCA genes but may benefit additional patients with different genetic profiles as well. BRCA genes are involved with repairing damaged DNA and normally work to prevent the development of cancer. The best way to incorporate PARP inhibitors into the overall management of ovarian cancer is being determined however they already have been shown to improve outcomes when used as maintenance therapy following completion of chemotherapy.3,4,5
Avastin® (bevacizumab: A targeted therapy that is showing promise in the treatment of ovarian cancer is Avastin®.6 Avastin slows or prevents the growth of new blood vessels by inhibiting a protein known as VEGF; this deprives the cancer of oxygen and nutrients. Avastin may also improve the delivery of chemotherapy to cancer cells by normalizing blood supply.
Intraperitoneal (IP) Chemotherapy: This treatment approach delivers chemotherapy directly into the abdominal cavity, where there is the greatest number of cancer cells. The chemotherapy is administered through a large catheter that is placed into the abdomen during the surgery to remove the cancer. This treatment appears to be most effective if surgery or other therapy has already reduced the size of any remaining cancer deposits to less than 1 cm, or about half an inch (this is often referred to as “optimally debulked”).
Among women with optimally debulked Stage III ovarian cancer, a phase III clinical trial compared treatment with intravenous (IV) chemotherapy alone to treatment with both IV and IP chemotherapy. Women who received both IV and IP chemotherapy survived more than a year longer than women who received only IV chemotherapy, but also experienced more severe side effects.7,8
Maintenance Therapy: Consolidation therapy, also called maintenance therapy, refers to extra systemic therapy that is given after completion of standard adjuvant chemotherapy. Maintenance therapy with Taxol or the PARP inhibitor Zejula (Niraparib) have both been demonstrated to improve outcomes in select patients.3,9
Neoadjuvant Chemotherapy: Neoadjuvant chemotherapy refers to chemotherapy that is given prior to surgery. When surgery is performed after chemotherapy treatment, it is referred to as interval cytoreduction. Some doctors believe that neoadjuvant chemotherapy can reduce the size of the cancer, thereby allowing easier surgical removal and more effective results from the subsequent chemotherapy. Although ongoing work is being done to explore the neoadjuvant chemotherapy-surgery-adjuvant chemotherapy format, current results do not suggest that this format shows an advantage over the more conventional format of surgery followed by adjuvant chemotherapy. There are current clinical trials attempting to further define the answer to this question.
4 Shapira-Frommer R, Oza AM, Domchek SM, et al. A phase II open-label, multicenter study of single-agent rucaparib in the treatment of patients with relapsed ovarian cancer and a deleterious BRCA mutation. Journal of Clinical Oncology. 33, 2015 (supplement; abstract 5513).
5 Tesaro Inc., press release. Tesaro’s niraparib significantly improved progression-free survival for patients with ovarian cancer in both cohorts of the phase 3 NOVA trial. Available at: http://ir.tesarobio.com/releasedetail.cfm?ReleaseID=977524. Accessed July 6, 2016.
6 Genetech. (2016.) FDA Approves Genetech’s Avastin® (Bevacizumab) Plus Chemotherapy for a Specific Type of Advanced Ovarian Cancer. [Press release.] Can be retrieved from https://www.gene.com/media/press-releases/14647/2016-12-06/fda-approves-genentechs-avastin-bevacizu
9 Markman M, Liu PY, Wilczynski S et al. Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: A Southwest Oncology Group and Gynecologic Oncology Group trial. Journal of Clinical Oncology. 2003;