BY DEBORAH ABRAMS KAPLAN | PUBLISHED APRIL 01, 2019
Women with this disease are living longer, despite common recurrence.
When Luci Berardi received a stage 4 ovarian cancer diagnosis in October 2010, she did not want to know her chances of survival. The physician told her family she’d be lucky to make it through Christmas, but no one passed that on to her. “I knew I had cancer and needed chemotherapy. It was bad enough (that) I knew it was stage 4,” Berardi says. She focused on her treatment and healing and revamped her diet, while still teaching yoga and working part time doing administrative work for a dental practice.
About 85 to 90 percent of ovarian cancers are epithelial cancer. For those with stage 4 disease, “the statistics may say that 17 to 20 percent will survive five years, but it’s not zero,” Berardi says. “People survive.” Survival rates are higher for other ovarian cancers — for all types, the five-year relative survival is 47 percent. If the disease is found early and has not spread outside the ovary, that rate jumps to 92 percent.
Like Berardi, women are living longer with ovarian cancer, and it’s increasingly seen as a chronic disease. Front-line, or initial, treatment hasn’t changed much in the past decade. But in recent years, new treatments have been added to the mix. These include oral therapies instead of IV; combination, immuno- and anti-angiogenic therapies; and PARP inhibitors. Most of these are for recurrent disease and may be based on genetic testing results. For the estimated 22,530 women a year who receive an ovarian cancer diagnosis in the United States, this is good news. Testing for genetic mutations may look at inherited mutations, which a person is born with, and show a higher likelihood of cancer risk. Genetic testing can also be done on the tumor tissue, showing genetic changes that were acquired later, and results may indicate whether specific treatments are more likely to help.
THE STANDARD APPROACH
About 75 percent of women with ovarian cancer receive their diagnosis when the disease is stage 3 or 4. “The majority of them can be treated with curative intent,” says Pam Khosla, M.D., section chief of hematology and oncology at Sinai Health System in Chicago. That includes debulking surgery, in which surgeons remove as much as they can of the visible tumors and cancerous tissue. Microscopic cancer cells and cancerous tissue that can’t be surgically removed are then treated with chemotherapy — typically, carboplatin and Taxol (paclitaxel).
Some doctors recommend surgery before the standard six cycles of chemotherapy, whereas others recommend three cycles, surgery and then three more cycles. Surgery may be the first step if the tumor is causing pain or physical issues, such as a bowel obstruction, or the physician is unsure whether cancer is causing the problems.
That was the case for Erica Roberts. In December 2015, she had abdominal cramping so severe, she thought her appendix was bursting. A trip to the emergency room and radiology imaging led the physician to believe she had an ovarian cyst. Only during the operation several weeks later did he realize she had stage 3A high-grade serous carcinoma, and he removed her ovaries and affected organs.
Not all patients are candidates for surgery — maybe the cancer is too extensive or the surgeon doesn’t think enough diseased tissue can be removed. The patient would typically receive chemotherapy every three weeks — two weeks on, one week off — or weekly, depending on the oncologist. After three cycles (or nine weeks) of treatment, imaging is repeated and cancer antigen (CA) 125 — a protein found in the blood — is measured. A CA 125 blood test can indicate a rise in ovarian cancer growth and determine how well the patient is responding to chemotherapy. If chemotherapy is working, patients who have not yet had surgery may be scheduled.
In June 2018, the Food and Drug Administration (FDA) approved Avastin (bevacizumab), a targeted therapy that belongs to a class of drugs called angiogenesis inhibitors, to use with chemotherapy and then alone for about a year, for women with stage 3 or 4 ovarian epithelial cancer that has been surgically removed. It was shown to increase the average amount of time before a recurrence. “To date, it hasn’t led to improvement of overall survival, but it keeps the cancer in remission four months longer than not using it,” says Ursula Matulonis, M.D., director of gynecologic oncology at the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute in Boston.
MAINTENANCE AND SUBSEQUENT TREATMENTS
About 70 percent of women with ovarian cancer will face a recurrence, according to the Ovarian Cancer Research Alliance. However, recurrence also varies by stage of disease. Maintenance therapy can help prevent the cancer from returning after the completion of chemotherapy. Up until a few months ago, Lynparza (olaparib), a PARP inhibitor, was approved only for patients who had a recurrence. But in December 2018, the FDA approved the oral medication as a first-line maintenance treatment for women with BRCA inherited (familial) genetic mutations — BRCA1 and BRCA2 raise a person’s risk of developing certain cancers, such as ovarian, breast and prostate — and advanced-stage disease. The drug targets an enzyme inside cancer cells to make it less likely that the cancer cell will repair itself, resulting in cell death. “It’s shown impressive results,” Matulonis says, with an increase of three years in progression-free survival compared with placebo.
Regardless of BRCA mutation status, PARP inhibitors were already approved as a maintenance strategy, says Maurie Markman, M.D., president of medicine and science and a medical oncologist with Cancer Treatment Centers of America in Philadelphia. The PARP inhibitor Rubraca (rucaparib) is approved for women with BRCA-positive advanced ovarian cancer who received multiple lines of chemotherapy treatment, and Zejula (niraparib) was approved after subsequent chemotherapy, no matter the BRCA status.
Although chemotherapy is the standard initial treatment, it doesn’t work for everyone. Diane Davis learned of her stage 2C ovarian cancer diagnosis in January 2017. After having 18 inches of her sigmoid colon removed because of tumor involvement, she began chemotherapy. Three cycles in, she felt just as bad as she had before surgery. Radiology studies showed that the cancer had grown back, spreading into her lymph nodes. “I was dumbfounded,” she says. “No one ever says people don’t make it through chemo.”
Genetic testing revealed that her tumor was microsatellite instability high (MSI-H) — cancer cells that have a greater than normal number of genetic markers and respond well to immunotherapy. Although immunotherapy has not been highly successful with ovarian cancer, Keytruda (pembrolizumab) was approved in 2017 for adult and pediatric patients with unresectable or metastatic solid tumors identified as MSI-H, just at the time she needed it. Davis started the two-year treatment that June, and in August, a CT scan showed that the new tumor was gone and the lymph node tumors shrunk. “We all cried,” Davis says. “My doctor said he’d never seen anything like it.”
IMPORTANCE OF GENETIC TESTING
Genetic testing should be done on all patients at the start of treatment, Matulonis says. This often involves blood tests that look at hereditary mutations. “Right now, there are at least 11 implicated genes for high-risk transmission,” she says. She recommends including as many genes as possible in the testing panel, not just the BRCA mutations. A genetic panel also covers Lynch syndrome, an inherited condition that increases a person’s risk of developing cancers such as colon, endometrial and ovarian and is linked to several gene alterations. Davis is living with Lynch syndrome. In addition to those that are inherited, mutations can also be acquired in the tumor.
Tumor assays can be used that may point to experimental therapies that attack the cancer’s vulnerabilities.
Although genetic testing is now highly recommended, not all patients think to ask for it. “A lot of people in my local support group hadn’t heard of it,” Davis says. “It’s important — not only knowing that you might have a genetic mutation that could give you other types of cancer but (also) to know (about) other treatments available. If my doctor hadn’t done testing on my tumor, I couldn’t get immunotherapy, and I’d not be talking to you today.”
Berardi also found genetic testing helpful. When she had a recurrence in 2014, her doctor recommended chemotherapy because she did well on it previously. She heard about genetic testing and sent a tissue sample from the baseball-size tumor the surgeon found during surgery. The genetic profile showed that the standard chemotherapy would not work well for the tumor. Instead, her doctor gave her etoposide, a chemotherapy less commonly used in ovarian cancer. It put her in remission, with no evidence of disease.
UNDERSTANDING PALLIATIVE CARE
Living with a chronic disease may affect a person physically and mentally. For instance, chemotherapy-related fatigue and nausea are common. Women with ovarian cancer also face sexual health concerns, such as painful sex, libido loss, early menopause and infertility. All these symptoms can lead to mental health issues such as depression and anxiety.
Through palliative care, health care providers can help patients through these concerns and improve their quality of life. “Palliative care doesn’t mean hospice,” Markman says. “‘Palliate’ means ‘to improve, to make better.’” He prefers the term “supportive care.” The goal of palliative care is to prevent or treat the symptoms of the disease as early as possible, according to the National Cancer Institute.
Patients within Sinai Health System meet with a multidisciplinary team, including a pharmacist, supportive oncology coordinator, nurse navigator and behavioral therapist, to schedule care, answer questions and address any issues, Khosla explains. Using this team approach has both improved patient satisfaction and quality of life and reduced hospital visits. Some hospitals reserve the palliative care specialists for those whose lives are heavily affected by treatment, though nurses and oncologists are trained to help with symptoms. “If you’re feeling side effects, chances are they have something to help you get better,” Roberts says of her oncology nurses. “You don’t get a gold medal for going through chemo without taking pain pills.”
Receiving palliative care can improve more than how a person feels, according to a study published in Annals of Behavioral Medicine, which showed that it can keep patients alive longer. Researchers analyzed studies that compared patients with advanced cancer who received palliative care with those who didn’t. They found that the palliative care group lived 4.5 months longer.
LIVING IN REMISSION
As many as 20 percent of patients with advanced stage disease have no recurrence after front-line therapy. Still, life after treatment doesn’t necessarily bring a sense of relief, especially when it’s time for periodic CA 125 testing.
Roberts finished her front-line treatment in 2016, including surgery and IV and intraperitoneal chemotherapy. She’s been in remission since. “The closer I get to the three-month checkup, the drumbeat gets louder,” and she thinks about the cancer constantly, she says. In addition to taking medications to handle her anxiety, she sees a counselor and goes to a Gilda’s Club support group. “The physical scars are just about healed. The emotional footprints are left,” she says.
Although difficult, the treatment process can still make women feel tended to. Once chemotherapy finished, Carol Hyman felt a cloud hanging over her — she felt alone and concerned about recurrence. “Even though the chemo is terrible, you’re being taken care of; you’re checked on continuously,” she says. Hyman received a stage 3B diagnosis when she was 65. Physicians found three large tumors and removed about a dozen lymph nodes.
In addition to finding her own support network, Berardi changed her diet. She sees a naturopath to get high-dose vitamin C infusions and supplements to reduce inflammation. She eliminated processed sugar and dairy and decreased her intake of carbohydrates. She takes a small amount of naltrexone and metformin, prescribed by her naturopath, in hopes of preventing recurrence. Patients sometimes use naltrexone at low doses to inhibit cancer growth and balance the immune system. Metformin targets stromal inflammation, which may provide resistance to cancer growth. Neither is approved by the FDA for ovarian cancer treatment because of lack of clear proof from controlled clinical trials, but anecdotal evidence suggests that some patients may benefit from these medications. “I’m trying to create an internal environment that is not conducive for the cancer to survive,” Berardi says.
Although she has had two recurrences, she says, the experience was in a way a blessing. “It took some of the anxiety away,” Berardi says. “My mindset now is that it’s a chronic disease, nothing different than high blood pressure or diabetes. You have to monitor it.” She also wrote a book, “Chasing Rainbows: My Triumph Over Ovarian Cancer,” because she was unable to find that sort of resource when she first received her diagnosis.
Hyman also finds support groups comforting. At her first meeting, she realized that every woman there had had at least one recurrence. Even though that talk can be scary, Hyman says, it gave her hope. One woman’s comment left a lasting impact: “I’m not dying from ovarian cancer — I’m living with ovarian cancer.”
SOURCE: CureToday.com
