People with ovarian cancer are usually treated first with a combination of chemotherapy and surgery. This initial treatment often causes the cancer to shrink or disappear. Unfortunately, around 70 percent of women with advanced ovarian cancer have a relapse within three years. One way to delay relapse is by using maintenance therapy, which helps keep the cancer under control for as long as possible. Maintenance treatments can extend the amount of time it takes for the cancer to come back or to start growing again.
The U.S. Food and Drug Administration (FDA) has approved two types of ovarian cancer maintenance treatments: angiogenesis inhibitors and poly (ADP-ribose) polymerase inhibitors — usually called PARP inhibitors. Each of these classes of medications work in different ways to slow the growth of tumors.
Angiogenesis is the scientific term for the creation of new blood vessels. Angiogenesis is the process by which the body makes new arteries and veins during normal growth and development, as well as during wound healing. Angiogenesis begins with chemical signals, including a molecule called vascular endothelial growth factor (VEGF). When VEGF attaches to certain cells, those cells begin creating new vessels. Blood vessels deliver oxygen and nutrients to cells throughout the body. Without oxygen and nutrients, cells cannot grow.
While angiogenesis is an important part of normal body function, tumors can take over this process for their own benefit. Cancer cells can make VEGF, leading the body to create new blood vessels that feed the tumor cells. A lot of scientific research has gone into creating drugs that can block tumor cells from using angiogenesis.
Avastin (bevacizumab) is a medication that attaches to VEGF. Avastin blocks VEGF from starting angiogenesis, which helps keep tumors from growing larger by starving the tumor. In some cases, Avastin can also help shrink tumors. Avastin is administered by an intravenous (IV) infusion every two to three weeks. Some people with ovarian cancer receive Avastin along with their chemotherapy. Avastin may also be used by itself as maintenance therapy after chemo.
PARP inhibitors are drugs that affect the way the body’s cells repair damage. In particular, they affect cells’ ability to fix damage done to DNA. The cell has several different methods of DNA repair.
One of these methods uses a molecule called poly (ADP-ribose) polymerase, or PARP. Cells use PARP to fix DNA when it breaks. Some cancer cells may be extra reliant on using PARP to heal themselves. PARP inhibitors are drugs that block PARP, which in turn prevents cancer cells from using this method of DNA repair and makes them more likely to die. PARP inhibitors that may be used for ovarian cancer maintenance treatment include Zejula (niraparib), Rubraca (rucaparib), and Lynparza (olaparib).
Another method of DNA repair uses BRCA1 and BRCA2 genes. Some people have mutations in the BRCA genes that prevent this pathway from working well. People with these mutations are more likely to develop certain cancers, including ovarian cancer and breast cancer — but when they do, their cancer cells have a weakness because they aren’t as able to repair their DNA. Tumor cells with BRCA gene mutations often die more easily when they are treated with drugs that block other DNA repair methods, such as PARP inhibitors.
PARP inhibitors come in the form of a pill or capsule. They may be used in different situations, for instance:
Read more about what to expect while taking ovarian cancer maintenance treatment.
The different types of maintenance therapy work better for certain groups of people. Doctors choose these medications based on how advanced the cancer is, what treatments have been tried, and which gene mutations are present in the tumor.
One of the first studies to test angiogenesis inhibitors for maintenance therapy was called ICON7. This trial included over 1,500 women with ovarian cancer. One group received chemotherapy. The other group received chemotherapy plus the angiogenesis inhibitor Avastin, and then they continued to take Avastin once chemotherapy was done. Cancer took longer to come back in the people who took the angiogenesis inhibitor. Women who were more at risk for worsening cancer saw the most benefit. They stayed cancer-free for longer periods of time and lived around eight months longer.
After this first study, doctors began prescribing angiogenesis inhibitors more often to treat ovarian cancer. In the beginning, people took these drugs for just a few months, but soon researchers learned that longer treatment led to even more benefit. Recent research has also found that angiogenesis inhibitors can lead to longer life for people with tumors that shrink when treated with platinum-based chemotherapy.
These trials found the most common side effect of angiogenesis inhibitors was high blood pressure. However, this condition was usually mild and could be easily treated. Other issues included tiredness, digestive problems, and high levels of protein in the urine.
A few PARP inhibitors have also been studied as possible maintenance therapies. Zejula was studied in people who had already gone through platinum-based chemotherapy with good results. Like many other trials studying maintenance therapies, this trial judged success based on progression-free survival (PFS). This term measures how long it takes for a cancer to get worse or come back. Zejula led to a longer PFS, meaning that cancer took longer to grow back. Zejula worked especially well for people who had a BRCA mutation.
The most common side effects experienced by people in this trial were anemia (low red blood cell counts), thrombocytopenia (low platelet counts), and neutropenia (low numbers of neutrophils, a type of white blood cell).
Another trial called ARIEL3 studied the PARP inhibitor Rubraca in people with ovarian, peritoneal, or fallopian tube cancer. People with BRCA mutations had the longest PFS after taking Rubraca, meaning they saw the most benefit from this therapy. People who had other genetic mutations that led to problems with DNA repair also had a longer PFS. Even people who had tumors with normal DNA-repair abilities saw a benefit from Rubraca, although not quite to the same extent.
Participants in this trial also often experienced anemia, as well as nausea and headache.
The PARP inhibitor Lynparza is also used to treat ovarian cancer. One early study of Lynparza only looked at people with BRCA mutations. In this trial, Lynparza lowered a person’s chance of dying or of having their cancer come back by 70 percent. Women who took Lynparza lived about three years longer. Overall, the study found Lynparza was fairly safe. The side effects were mostly minor and were similar to those seen with other PARP inhibitors. Whether people received Lynparza or not, they had a similar long-term quality of life. However, a few women — equaling 1 percent of the women participating in the trial — developed blood cancer, such as leukemia, after treatment.
After this initial trial, several additional trials confirmed these results. Some studies expanded the results by asking whether Lynparza was also useful for women who did not have BRCA mutations. In two similar clinical trials, Lynparza lowered a person’s chance of dying or having their cancer get worse by 65 percent to 70 percent, whether they had BRCA mutations or not.
Doctors have started using angiogenesis inhibitors and PARP inhibitors together. Lynparza is now sometimes used along with Avastin for people living with advanced stage tumors. This gives people with ovarian cancer an additional option for maintenance therapy.
The FDA approved the use of this combination after researchers ran a clinical trial testing the two medications together. This study included 806 women who had ovarian tumors. All of the women had been previously treated with chemo that made their tumors shrink or disappear. Study participants all received the angiogenesis inhibitor, and half also received a PARP inhibitor. Women who took both drugs and had genetic mutations that weakened cells’ DNA repair saw a benefit. It took 19 extra months for their tumors to come back or get worse. On the other hand, women without these genetic mutations did not have a longer PFS. Study participants said that they experienced similar side effects regardless of which group they were in, showing that taking both medications together doesn’t seem to lead to worse negative symptoms.
Your oncologist can help you better understand which cancer treatments may be most likely to help you. If you’ve already gone through initial front-line therapy such as chemotherapy, maintenance therapy may be able to help keep cancer under control and give you more time before the cancer comes back. In some cases, maintenance treatments may help women live longer.
Read more about living well with ovarian cancer.
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