Patients who have been diagnosed with ovarian cancer may have persistent, refractory or recurrent cancer following initial treatment. Individuals with recurrent ovarian cancer can benefit from additional surgery, radiation therapy and systemic treatment with chemotherapy and/or poly ADP-ribose polymerase (PARP) inhibitors or other precision cancer medicines.1
- Persistent cancer refers to residual cancer growths or cells that persist during and following initial treatment.
- Patients who have achieved complete remission following initial therapy and who subsequently experience a return of cancer cells after treatment are said to have relapsed or recurrent cancer.
- Patients with ovarian cancer who experience progression or continued growth of the cancer during treatment are said to have refractory cancer.
Many patients with persistent, recurrent or refractory ovarian cancer can benefit from additional treatment with surgery and/or second-line systemic therapy, which is often referred to as salvage therapy. A patient’s treatment options will differ depending on whether the cancer is persistent, recurrent or refractory.
How is Recurrent Ovarian Cancer Detected?
Recurrent or persistent ovarian cancer may be detected by several methods. Some patients will experience abdominal swelling, pain or symptoms related to the spread of cancer cells (metastases) to the bone, liver, or brain. Other patients may simply have an increase or persistent elevation in the CA-125 level, a blood test commonly used to monitor ovarian cancer activity. When an increase in the CA-125 occurs, most patients will undergo ultrasound or CT scanning of the abdomen and pelvis or other diagnostic procedures in order to determine the location of recurrent cancer.
Does early treatment of a CA 125 recurrence improve outcomes?
The MRC OV05/EORTC 55955 clinical trial evaluated women in remission after first-line treatment for ovarian cancer. When CA125 was > 2x the upper limit of normal women either started chemotherapy treatment or waited until there was an objective reason to begin treatment and directly compared. Early treatment of a rising CA125 was associated with a more rapid decline in quality of life and no improvement in survival when compared to delayed treatment.2
What is the role of surgery in recurrent ovarian cancer?
Typically, women who have ovarian cancer are initially treated with surgery, followed by systemic chemotherapy. If the cancer recurs (returns) after treatment, additional systemic therapy may be used to increase survival time and relieve the symptoms of the cancer. Additional surgery to remove recurrent cancer combined with systemic therapy appears to further improve survival when compared to treatment with systemic therapy alone.
Additional systemic therapy for recurrent ovarian cancer
Because patients with recurrent ovarian cancer have cancer cells that have spread throughout the body and cannot be removed by surgery an effective treatment is needed to find and destroy these cells in order to prolong survival. Systemic therapy is treatment directed at destroying cancer cells throughout the body, and may include chemotherapy, precision cancer medicines, immunotherapy or a combination of these therapies. The effectiveness of additional systemic treatment depends on the kind of chemotherapy previously administered, the duration since last treatment and the extent of recurrent cancer.
- Persistent Ovarian Cancer
- Recurrent Ovarian Cancer
- Recurrence after 6 Months from Therapy
- Recurrence within 6 Months from Therapy
Patients with persistent ovarian cancer have cancer cells that are detected after initial surgery and first-line systemic therapy. Persistent ovarian cancer is detected either by an elevated CA-125 blood level, abnormal x-rays and CT scans, or with a biopsy performed during second-look laparotomy.
Individuals with persistent ovarian cancer have a number of treatment options. Additional debulking surgery to remove as much persistent cancer as possible should be considered before resuming additional systemic treatment. Even with additional surgery additional systemic treatment is still necessary since undetectable microscopic deposits of cancer still exist and cause recurrences even after successful debulking surgery. Patients should consider participation in a clinical trial evaluating new systemic treatment approaches.1
- Continued Standard Chemotherapy: The standard course of initial chemotherapy is approximately 6 cycles, or about 4 months of treatment. If, after 6 cycles, there is a small amount of persistent cancer, some doctors feel further chemotherapy treatment for 10 or 12 cycles may continue to cause shrinkage of the cancer. Some patients may achieve a complete remission with continued standard chemotherapy.
- Second-Line Therapy: Not all patients are able to undergo secondary debulking surgery or are expected to improve with continued treatment with their first-line treatment. Salvage or second-line systemic therapy with other anti-cancer drugs that destroy cancer cells by a different mechanism may provide additional benefit over the continuation of first-line Second line systemic therapy may consist of precision cancer medicines, immunotherapy, and/or chemotherapy medications not previously used or participation in a clinical trial evaluating altogether new medications and combinations.
Patients with recurrent ovarian cancer have experienced a period of “remission” following initial surgery and first-line systemic therapy but have subsequently developed a cancer recurrence. Both the effectiveness and type of available therapy depends on the first-line systemic therapy received, the length of time since finishing treatment and the extent of recurrent cancer.
In general, additional systemic therapy treatment is used to improve a patient’s quality of life by reducing symptoms of recurrent cancer and prolong survival.1
The length of time between the completion of first-line chemotherapy and the development of recurrent cancer affects treatment options. Patients who develop recurrent cancer more than 6 months after first-line chemotherapy can experience another remission following treatment with the identical first-line chemotherapy that was previously used. Patients who develop recurrent cancer within 6 months from first-line chemotherapy are less likely to improve with the same anti-cancer drugs and should consider treatment with a different chemotherapy regimen. All patients with recurrent cancer should also consider participating in clinical trials.
Patients who develop recurrent ovarian cancer more than 6 months after first-line platinum-based chemotherapy are referred to as “platinum sensitive” and have a good chance of improving with continued use of these drugs or treatment with a PARP inhibitor. Debulking surgery to remove as much cancer as possible may be considered before resuming treatment. Over half of patients who develop a recurrence longer than 12 months from initial treatment are likely to improve with further systemic treatment, compared with less than half of patients who develop a recurrence between 6 and 12 months from initial treatment.1
PARP Inhibitors:The poly ADP-ribose polymerase (PARP) enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. PARP inhibitors are a new class of precision cancer medicines that contribute to cancer cell death and increased sensitivity to chemotherapy. By blocking the PARP enzyme, DNA inside the cancerous cells is less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth.
PARP inhibitors have the greatest effect in women who test positive for BRCA and HRD genetic mutations but also appear to benefit patients with different genetic profiles as well.4,5,6 PARP inhibitors are effective when used in women with recurrent ovarian cancer who achieve a partial or complete response to platinum-based chemotherapy.2
Patients who develop recurrent cancer within 6 months from first-line systemic therapy are referred to as “platinum resistant” and less likely to improve with additional treatment that utilizes the same first-line drugs. Patients can derive significant benefit from additional treatment with additional systemic therapy or from participation in a clinical trial designed to evaluate promising new treatment strategies.
Avastin Plus Chemotherapy Improves Progression-Free Survival in Platinum-Resistant Recurrent Ovarian Cancer
Avastin (bevacizumab) is a targeted therapy that blocks a protein known as VEGF. VEGF plays a key role in the development of new blood vessels. By blocking VEGF, Avastin deprives the cancer of nutrients and oxygen and inhibits its growth. The addition of Avastin® to standard chemotherapy significantly can improve progression-free survival and objective response rate among women with platinum-resistant recurrent ovarian cancer.3
3 Pujade-Lauraine E, Hilpert F, Weber B, et al: Bevacizumab Combined With Chemotherapy for Platinum-Resistant Recurrent Ovarian Cancer: The AURELIA Open-Label Randomized Phase III Trial. Journal of Clinical Oncology. Published early online March 17, 2014. doi: 10.1200/JCO.2013.51.4489.
4 Mansoor R. Mirza, M.D et. al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer N Engl J Med 2016; 375:2154-2164.
5 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).
6 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: http://ir.tesarobio.com/releasedetail.cfm?ReleaseID=977524. Accessed July 6, 2016.