“We are truly in the Golden Age, the Renaissance, if you will, of care for people with ovarian cancer. So much is happening.”
Dr. Stephanie Blank
Image: Mount Sinai website
Though there is still much progress to be made when it comes to ovarian cancer therapies, breakthroughs in recent years have led to significant changes in how the disease is approached and treated — changes that hold promise for continued advancements in care.
This article is adapted from a presentation made at OCRA’s 2022 Ovarian Cancer National Conference by Dr. Stephanie Blank, Director of Gynecologic Oncology for the Mount Sinai Health System and a professor at the Icahn School of Medicine at Mount Sinai.
Tailoring treatment to ovarian cancer type
The arsenal of therapies has expanded substantially over the past decade, with more treatments available than ever before. As Dr. Blank pointed out, the U.S. Food and Drug Administration (FDA) has approved more ovarian cancer therapies since 2014 than in the 60 years prior combined.
It is not only the increase in the number of ovarian cancer therapies that is significant, but also the types that have been approved. In prior decades, the drug options were all forms of chemotherapy, a treatment that uses powerful chemicals to destroy or reduce cancer cells. In contrast, all ovarian cancer drugs approved by the FDA over the past decade or so are categorized as targeted therapies, also known as targeted agents. And though chemotherapy remains a mainstay in treating epithelial ovarian cancer (EOC), which is the most common type of the disease, these newer drugs show promise in helping to prolong survival for certain patients. These agents are typically given in combination with chemo during frontline treatment or after chemo as maintenance therapy.
Ovarian cancer targeted therapy
The drugs that are classified as targeted therapies have a major distinction from chemotherapy agents in that they attack specific cancer cells while leaving healthy cells largely untouched. Chemo drugs, on the other hand, not only kill cancer cells, but also healthy cells that rapidly divide, such as those found in hair follicles, bone marrow and the lining of the digestive system.
Targeted therapies that have been approved for ovarian cancer include the following:
- Parp inhibitors are targeted agents that speed up the death of ovarian cancer cells by keeping them from being able to repair themselves. These drugs block a protein in the body called poly adenosine diphosphate-ribose polymerase, or PARP, which helps fix mistakes in DNA. When the PARP protein is blocked, the cancer cells are unable to repair their damaged DNA, which are molecules that control cellular activity. The cancer cells die as a result, yet healthy cells are largely unaffected since they have a backup mechanism for fixing DNA. The three PARP inhibitors that have been approved for use with epithelial ovarian cancer are olaparib, niraparib and rucaparib.
- Angiogenesis inhibitors are drugs that essentially starve ovarian cancer tumors by slowing the growth of blood vessels. The development of new blood vessels in a process known as angiogenesis is an essential part of cancer growth, as solid tumors need a blood supply to thrive. Bevacizumab is a type of angiogenesis inhibitor that targets a protein in the body known as VEGC (vascular endothelial growth factor), which activates blood vessel growth that contributes to ovarian cancer. By binding to VEGC, bevacizumab blocks the development of new blood vessels. Bevacizumab is approved for the treatment of certain patients with epithelial ovarian cancer.
Ovarian cancer immunotherapy
Drugs that are categorized as immunotherapy agents help boost the body’s defenses, which are collectively known as the immune system, so that cancer cells can be destroyed more effectively.
- Monoclonal antibodies are created from cloned molecules developed in a laboratory that mimic the ones made naturally by the body’s immune system. Some monoclonal antibodies are considered both immunotherapy agents and targeted therapies, with bevacizumab being one ovarian cancer drug that is both. Other monoclonal antibodies are called checkpoint inhibitors and they enable tumor-fighting T cells to kill cancer cells. These drugs do so by blocking proteins known as checkpoints that become programmed by cancer cells to keep T cells from attacking. Pembrolizumab is one such drug. Used to treat certain patients with advanced epithelial ovarian cancer, pembrolizumab blocks the immune checkpoint known as PD-1.
Ovarian cancer chemo drugs
Even with the advent of targeted therapy and immunotherapy agents, chemotherapy continues to be the linchpin of ovarian cancer treatment. The standard of care treatment given to patients upon initial diagnosis of epithelial ovarian cancer has long been surgery aimed at removing as much of the tumor as possible followed by chemotherapy. But the order of the steps involved with this treatment paradigm has changed over the past couple of years, as Dr. Blank explained.
“Once somebody is diagnosed, we used to start everybody with surgery but now we know that there are certain patients that should start with chemotherapy. So that’s a big change,” said Dr. Blank. “The timing of chemotherapy is different.”
If a patient is given a course of chemo drugs before surgery, this is called neoadjuvant chemotherapy. If the treatment comes after surgery, it is referred to as adjuvant chemotherapy.
Regardless of the timing of the chemotherapy, a specific combination of drugs is typically used for this frontline treatment.
- Taxanes are chemo drugs that interfere with the process of cell division known as mitosis. And when cancer cells are no longer able to divide, they stop growing and die.
- Platinum-based drugs also cause the death of cancer cells by preventing them from growing. As the name suggests, these chemotherapy agents contain the chemical element platinum. They form highly reactive platinum complexes that bind to DNA and stop cell growth as a result.
- First-line chemo: Paclitaxel and carboplatin as frontline therapy
The current frontline treatment standard for advanced epithelial ovarian cancer involves a combination of paclitaxel, which is a taxane, and the platinum-based drug carboplatin. “We know that the vast majority of patients are going to have a complete response to this treatment,” Dr. Blank noted. And what is meant by complete response, as defined by the National Cancer Institute (NCI), is that all signs of the cancer disappear due to the treatment, though the patient may not necessarily be cured. In certain cases, targeted therapy in the form of bevacizumab is used in combination with chemo for frontline treatment.
Maintenance therapy for ovarian cancer
After this first-line therapy has been completed, some patients may benefit from maintenance treatment. “We don’t do surgery at the end of chemotherapy, which used to be done,” Dr. Blank explained. “You have this concept of maintenance: a drug that you take to solidify the response that you have obtained.”
Certain patients who are given bevacizumab in combination with chemo as part of their frontline therapy will also be treated with this drug as maintenance after they finish chemotherapy.
PARP inhibitors are also used in maintenance therapy, sometimes in combination with bevacizumab and sometimes on their own.
“When you think about maintenance, the goal is to maintain a response, so you have to have something that worked already and it’s generally pretty long-term,” Dr. Blank said.
Ovarian cancer survival rate
As an influx of new drugs has become available for not only first-line and maintenance therapies, but also for the treatment of recurrences, the overall survival rate for ovarian cancer has been steadily increasing. “Deaths are down 2.3% per year,” Dr. Blank noted. “People are living longer because we have better therapy for recurrent disease. We have more options.”
Ovarian cancer diagnosis rate
In addition to increased survival, less people are being diagnosed with the disease. The incidence of new ovarian cancer cases has been falling, with Dr. Blank noting that the rates are down by approximately 3.3% per year. Dr. Blank attributed this decrease in incidence partly to advancements in a type of testing that helps to determine if someone is at a higher risk for ovarian cancer due to genetic factors.
Genetic testing
A gene is a basic unit of DNA that contains information on hereditary characteristics, such as hair or eye color, as well as susceptibility to certain diseases. And genetic testing can determine if someone is carrying a gene change or mutation passed down by a parent that will cause an elevated risk of ovarian cancer.
The most common type of mutations linked to ovarian cancer are ones that occur in the BRCA genes associated with DNA repair: BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2). However, there are many more mutations that can cause ovarian cancer. As Dr. Blank pointed out, nearly one-third of ovarian cancer patients with mutations have these changes in non-BRCA genes.
Dr. Blank urged anyone who was assessed when panel testing first became widely available in 2013 to seek out genetic counseling to see if they should be retested because there have been significant changes since that time. Discuss with your doctor to find out what genetic counseling options are available to you.
“Even prior to diagnosis, we can identify people at increased genetic risk for ovarian cancer and prevent it,” she noted.
Preventing ovarian cancer
Though there is no way to completely prevent all types of ovarian cancers from developing in every case, risk-reducing surgery is oftentimes recommended for those found to have a greater propensity for developing the disease due to genetic mutations. “Once somebody is known to have a mutation predisposing them to ovarian cancer, a very effective way of preventing ovarian cancer is risk-reducing surgery,” Dr. Blank said.
Typically, the fallopian tubes and ovaries are removed in a procedure known as a bilateral salpingo-oophorectomy.The removal of the ovaries will put the patient into immediate menopause. As such, this procedure is recommended for high-risk women who are done having children, according to the American Cancer Society. A bilateral salpingo-oophorectomy has been shown to dramatically decrease ovarian cancer risk in women with a BRCA1 or BRCA2 mutation, with the NCI stating that a 90% reduction in risk has been observed.
Researchers are currently studying whether early menopause can be avoided while achieving this same level of ovarian cancer risk reduction by leaving the ovaries intact but removing the fallopian tubes in a procedure known as a bilateral salpingectomy. Known as the SOROCk study, this research project focuses on women between the ages of 35 – 50 who have a BRCA1 mutation. “We actually think a lot of these ovarian cancers arise in the [fallopian] tube,” Dr. Blank explained. “We believe that if we remove the tube preventatively, we can reduce cancer risk without putting people into menopause.”
Learn more about the connection between the fallopian tubes and ovarian cancer.
The option of removing fallopian tubes may also be offered to patients who do not have a known risk of ovarian cancer but are having pelvic surgery for another reason, such as a hysterectomy for fibroids. Various professional organizations recommend that this procedure, called an opportunistic salpingectomy, be used for the general public as a preventative measure against the most common subtype of the disease known as high-grade serous ovarian cancer (HGSOC). “Remember that most people who have ovarian cancer do not have a genetic predisposition,” said Dr. Blank, explaining that this procedure is meant to help protect those who would not have been getting their fallopian tubes out due to a known increased risk of ovarian cancer. Results from a retrospective cohort study published in 2022 found that not a single serous ovarian cancer had developed in the patients who had undergone an opportunistic salpingectomy, as compared with 15 serous cancers in the control group.
Read about additional ways to reduce ovarian cancer risk.
All treatment and preventative options for ovarian cancer should always be discussed with your doctor. And it is of critical importance that anyone diagnosed with ovarian cancer consult a gynecologic oncologist, as research shows that being treated by one significantly improves survival advantages for patients. Learn more about gynecologic oncologists.
