September is Ovarian Cancer Awareness Month
- September is Ovarian Cancer Awareness Month, and gynecological oncologists tell SurvivorNet that right now is an exciting time for advancements in treating this type of cancer. PARP inhibitors are changing the way the disease is treated.
- Dr. Monica Vetter tells SurvivorNet that these drugs are typically used as maintenance therapy — to prevent the cancer from recurring or progressing after surgery and traditional chemotherapy. PARP inhibitors can be used during the first diagnosis of ovarian cancer as a maintenance medication, or used as a maintenance drug with recurring ovarian cancer.
- Ovarian cancer has been called the “cancer that whispers” since women often don’t experience symptoms until their cancer has reached its late stages. Vetter tells SurvivorNet that most ovarian cancer cases are diagnosed in stage 3 or stage 4, as it’s a difficult cancer for which to screen. She says that about 70% to 80% of those women are going to have their cancer come back within the first five years.
“I think it’s a really exciting time for ovarian cancer treatment advancements,” Dr. Monica Vetter, a gynecological oncologist at Baptist Health Medical Group in Lexington, Ky., tells SurvivorNet. “For a long time there really weren’t many changes or advancements (in treatment), which was really frustrating for people.”Read More
PARP Inhibitors: What They Are and How They Work
What are these new advancements that have doctors buzzing? PARP inhibitors.
PARP stands for poly (ADP-ribose) polymerase, and these drugs are relatively new to cancer care. The first PARP inhibitor drug, olaparib, was approved by the U.S. Food and Drug Administration in 2014 for BRCA-mutated carriers — BReast CAncer (if you’re confused, don’t worry, we touch on this gene mutation later on) — who had progressed on more than three lines of therapy; this means that someone had to have had cancer that progressed or worsened on three previous forms of therapy. The drug was approved by the FDA in 2018 to be used for first-line maintenance.
There are now three FDA-approved PARP inhibitor drugs for ovarian cancer — olaparib, sold under the brand name Lynparza; niraparib, sold under the brand name Zejula; and rucaparib, sold under the brand name Rubraca. These medications are taken orally and work by preventing cancer cells from being able to repair DNA damage, which then leads to cell death.
“These medications are exciting because they’ve been studied in different patient populations and different settings,” Vetter says of PARP inhibitors.
Vetter explains that these drugs are typically used as maintenance therapy — to prevent the cancer from recurring or progressing after surgery and traditional chemotherapy. PARP inhibitors can be used during the first diagnosis of ovarian cancer as a maintenance medication, or used as a maintenance drug with recurring ovarian cancer.
When used this way, PARP inhibitors can potentially prolong ovarian cancer remission and prevent a recurrence of the disease for an extended period of time — in some cases, even for good, Dr. David Engle, a gynecological oncologist at Baptist Medical Group in Memphis, Tenn., tells SurvivorNet.
“PARPs are probably the most exciting advancement (in treatment) really,” Vetter says.
Dr. Dana Chase, a gynecological oncologist at Arizona Oncology, tells SurvivorNet that besides PARP inhibitors, there hasn’t been much further development when it comes to FDA-approved ovarian cancer treatments. But she did say there are a lot of promising clinical trials happening right now. If she has a patient she knows won’t respond as well to PARP inhibitors or other ovarian cancer treatments used over the last few decades, she’ll recommend a clinical trial.
“Clinical trials are still very much at the beginning,” she says of ovarian cancer treatment research. “I would say to patients that there’s this awesome website, clinicaltrials.gov; they can look for trials in their area (on the website.) That’s always worth asking for.”
Now, what is the BRCA1 (BReast CAncer gene 1) or BRCA2 (BReast CAncer gene 2) gene mutation, you ask? These genes help cells repair their DNA damage. Having a change, or mutation, in one of these genes increases a woman’s risk of getting ovarian cancer. These gene mutations are commonly passed down in families; if a parent carries a BRCA gene mutation, there’s a 50-50 chance you could be carrying it too.
The BRCA gene stands for breast cancer, meaning a woman’s chances of developing breast cancer are increased, but Chase tells SurvivorNet it can also include increased risk for other cancers like ovarian cancer or pancreatic cancer. “It can sometimes even be associated with other cancers,” Chase says.
Women with the BRCA1 gene have a 30% to 40% risk of ovarian cancer, while women with the BRCA2 gene mutation have a 10% to 20% risk of developing this type of cancer. Vetter says between 15% and 20% of ovarian cancer patients are going to have this genetic defect, and those patients do “outstanding well” with PARP inhibitors; there’s another class of patients that don’t have the BRCA gene. It’s called homologous recombination deficiency, or HRD.
Homologous recombination deficient (HRD) tumors are tumors in which the cancer cells are less efficient at repairing DNA. Similar to patients with the BRCA1 or BRCA2 gene mutations, someone with HRD positive testing is more likely to respond to a PARP inhibitor drug.
Other Ovarian Cancer Treatments
For decades, Vetter explains, the combination of two chemotherapy drugs called carboplatin and paclitaxel have been the backbone of ovarian cancer treatment. The most common chemo drug for ovarian cancer patients is a platinum-based agent, such as carboplatin, cisplatin or oxaliplatin.
Patients with ovarian cancer will typically receive another chemo drug called a taxane in combination with their platinum-based drug. The taxane drug used most often in the United States is called paclitaxel, which is often known as Taxol.
This treatment method was the “gold standard” and only FDA-approved treatment for this type of cancer for about 20 years, until 2010. One of the first medications to get approval over the last decade, Dr. Vetter says, was bevacizumab, which is sold under the brand name Avastin.
“That led to FDA approval for recurrent ovarian cancer and newly diagnosed ovarian cancer,” Vetter says. “It’s an interesting medicine because it’s a little different than traditional chemotherapy — it works by impacting blood vessel formation; it prevents tumor cells from creating new blood vessels.”
Bevacizumab is used as a combination drug with chemotherapy and then as a maintenance drug, Vetter says. Bevacizumab blocks a certain protein called a “vascular endothelial growth factor,” which helps tumors grow, Dr. Beth Karlan, a gynecological oncologist at UCLA Medical Center, tells SurvivorNet. In other words, rather than killing cancer cells themselves, as chemo does, bevacizumab chokes the cells at their roots, limiting blood supply to the tumor cells.
Since the FDA-approval of bevacizumab, PARP inhibitors have been the next big breakthrough in ovarian cancer treatment, according to Vetter. In 2020, using a PARP inhibitor with bevacizumab was approved by the FDA, so the usage of this treatment for ovarian cancer is relatively new.
“I use them (PARP inhibitors) in my practice,” Vetter says, “I think at this point most gynecological oncologists use PARP inhibitors.”
‘Cancer That Whispers’
Ovarian cancer has been called the “cancer that whispers” since women often don’t experience symptoms until their cancer has reached its late stages. Vetter tells SurvivorNet that most ovarian cancer cases are caught in stage 3 or stage 4, as it’s a difficult cancer for which to screen. She also says that about 70% to 80% of those women are going to have their cancer come back within the first five years.
There isn’t just one ovarian cancer; there are many different types that occur at different stages of life. Researchers have identified more than 30 types, but these three are the most common:
- Epithelial — about 90% of ovarian cancers are epithelial, which means the cancer cells are located on the outer layer of the ovary. Most epithelial tumors are not cancerous, but when they are cancerous, they can spread before they are detected.
- Stromal — this rare type of tumor forms in the connective tissue that holds the ovary together and produces estrogen and progesterone.
- Germ cell — these tumors, which develop in the cells that produce the eggs, are more likely to affect a single ovary, rather than both ovaries. When a teen or young woman is diagnosed with ovarian cancer, it’s usually the germ cell type. Most women with these types of ovarian cancers can be cured.
There are various reasons a woman could be at risk of developing ovarian cancer, but one is having the specific BRCA1 or BRCA2 gene mutation; another is HRD, which we touched on earlier.
Fifty percent of patients don’t have the BRCA or HRD (that’s called HRP — homologous recombination proficiency, the opposite of deficiency) gene mutations, Vetter says, and sometimes, the data for patients who have neither mutation doesn’t get published. “The tough part is that most of the studies didn’t look at this specific group of patients”; they were lumped into the overall cohort.
Chase says that for those 50% of patients, she will usually recommend a clinical trial of some sort when it comes to treatment. With HRP patients, those women are platinum therapy resistant as well. “(For) those women, there are a lot of active clinical trials with drugs that work in many different ways,” Chase says. PARP inhibitors can still be used for those women, “but is the outcome going to be as good?” Chase says she asks herself when deciding on a treatment plan.
“I use PARP inhibitors a lot; a lot in the BRCA mutated group and HRD (and) non-BRCA group,” Chase says. “In the other group, (patients) that are not HRD or BRCA, I will use PARP as well, but I won’t expect as good of results. If there’s a clinical trial, I’ll go to that because I know I have to do better for those women.”
“How are we making PARPs better for (that) 50%,” Vetter says. “I think that’s where the research is going.”