Thursday, August 22, 2019

Ovarian Cancer's New Identity: A Chronic Disease

This article was originally posted CURE Today on April 1, 2019. Written by Deborah Abrams Kaplan
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.
Luci Berardi says she views her disease no different than someone who has high blood pressure or diabetes.

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."

Wednesday, August 21, 2019

Donna Wiegle: Leaving on her Cross-Country Trip To Raise OC Awareness























August 18, 2019by Donna WiegleOrganizer




Just 9 days left until I depart for Coos Bay, Oregon. Last I heard my bike had made it as far as Columbus, OH, expecting to be delivered at Highway 101 Harley Davidson on August 23. I arrive on August 27 and if all goes well on my travels across the country I will begin my ride the following day.

My fundraising is going amazingly well!!! I am just $91 short of $28,000!!!! It is unbelievable how generous both people I know, and those I don't know have been! It's so heartwarming to have so many people supporting me and my mission.

Speaking of support, you can see from my picture here that I am sporting my new black leather vest with my TEAL on WHEELS patch on the back. A lovely lady from Cherryfield, Downeast Maine, sewed the patch on for me and would't accept any payment! I had the same thing happen when Les Foss inspected my teal and white bike...no money exchanged hands. Also, when I got the bike serviced by Stanley Gardner at Gardner Racing Concepts...Stanley provided all the parts and labor free of charge to support me.  

It's crunch time now and I still have a long list of things to do, but each day I am making progress towards my departure date. I am excited, nervous, and just a little bit scared! I know everything will work out just fine. I packed 1,000 ovarian cancer symptoms cards rubberbanded in packs of 25, then packed in ziplock bags in my saddlebags of my bike. I hope to distribute every last one on my way across the United States.

If you want to follow my trip, go to tealonwheels.org and subscribe to my blog on the bottom of the home page. I will be posting frequently from the road.

Thank you for all of your support. It means the world to me!

To donate to Donna's campaign to raise awareness about the signs and symptoms of ovarian cancer, go to this linkhttps://www.gofundme.com/f/teal-on-wheels-ovarian-cancer-awareness-tour


Register for the Ovations 13th Annual Learning for Living Symposium on Sept. 14, 2019

This is always such a great event that is free to women and their guests. The day begins with breakfast at 8 a.m. followed by presentations by leading ovarian cancer experts and then lunch. Parking is at a reduced rate.

To find out more about this important event and to register, follow this link

Thursday, August 15, 2019

Nirapamib for Maintenance Therapy: New Evidence that All OC Women Would Benefit

When I was diagnosed 4 years ago options for maintenance therapy were generally limited to women who were BRCA+.  Not so any more with this particular PARP. Avastin was also available but the data was not strong enough to support me being on it, according to my surgeon. I was Stage 3C and the plan was for me to undergo surgery followed by IV/IP treatment, all of which I completed.

Maintenance therapy is becoming more standard however and so, four years out, there is  nothing in the article to suggest that women like me begin maintenance.

This article by Dr. Oliver Dorigo from Stanford University Medical Center, was found on Survivornet.com. Here's what Dr. Dorigo has to say about Nirapamib:

After undergoing surgery and getting chemotherapy for ovarian cancer, you may want to consider taking a relatively new kind of drug called a PARP inhibitor, which helps to kill off cancer cells. “PARPs” are somewhat recent entrants into ovarian cancer treatments and are getting lots of attention from oncologists.
What are PARPs For?
While PARP inhibitors were originally approved to treat cancer recurrence in BRCA mutated patients with at least 2 or 3 prior lines of chemotherapy, there is compelling new evidence that all ovarian cancer patients, regardless of BRCA mutation, may want to consider PARP inhibitors for maintenance if they’re responding well to chemotherapy (including a platinum drug such as Carboplatin).
We spoke to Dr. Oliver Dorigo, a Gynecologic Oncologist at Stanford Medical School, about some of the details:
Niraparib as late-stage therapy for women without BRCA mutations:
Niraparib, also known as Zejula, is one of the three major PARP inhibitors, and can be used in patients without BRCA mutations (about 80% of women). According to Dr. Dorigo, “We have trials that have shown that Niraparib in any patient with [ovarian cancer] can be beneficial in the maintenance setting…independent of a BRCA mutation.” Tumor cells with BRCA mutations have problems repairing DNA already, and the PARP inhibitors make these cells even less functional, causing cancer cells to die. Nonetheless, Niraparib has been shown to be effective in patients without this mutation. The other two PARP inhibitors, Olaparib and Rucaparib, are also approved to be used in this setting with the same indications.
The drug is currently approved for use as maintenance therapy for advanced/recurrentovarian cancer patients, regardless of whether they have BRCA mutation. These patients have undergone initial surgery and multiple rounds of chemotherapy, but their cancer continues to come back. In fact, in one trial known as the NOVA trial, patients without BRCA mutation who had already undergone several rounds of chemotherapy lived more than twice as long after taking Niraparib as those who did not. Niraparib, like other PARP inhibitors, is used to block the ability of tumor cells to repair DNA, thus eventually killing them.
Niraparib as an ‘up-front’ therapy for women without BRCA mutations:
Niraparib is also being tested in a clinical trial for use after just the first line of chemotherapy. Doctors refer to PARP inhibitors used at this early stage in the treatment course as the drug being given ‘up-front.’ According to Dr. Dorigo, the trial, called the PRIMA trial, is looking at whether Niraparib can be used in ovarian cancer patients directly after the first round of chemotherapy following surgery, regardless of whether they have a BRCA mutation. Although the results have not been presented or published yet, Dorigo and other specialists believe that there is hope for the use of this drug in this setting.


Tuesday, August 13, 2019

Evaluating Bevacizumab and PARP Inhibitors as Important Treatment Options

The following is a transcript by Dr. Michael Birrer, taken from Survivornet.com. Dr. Birrer, formerly medical director of gyn/onc and the gyn/onc research program at MGH, is now at the University of Alabama.

How do you decide what patients should get bevacizumab versus PARP? And that's really the million dollar question, and it's a very unique question. 
For those of us treating ovarian cancer patients, for almost 20 years, all we had was Carboplatin and Taxol. 
And we would argue about what taxane to use, or we might argue about IP versus IV. 
But there weren't really earth-shattering questions. 
Now we have choices, so it's terrific for the patients. 
But nevertheless, one needs to make that choice. 
And I think that the field is migrating that if patients have either germline or somatic BRCA1 gene mutations, that when possible, they should get a PARP inhibitor. 
However, you need to recognize you're looking at about 20% of the patient population. 
The other 80%, you need options. 
And there is where one might consider bevacizumab. 
Now does everybody get bev? Probably not, if you have certainly tumor infiltrating the bowel or other contraindications that might be risky. 
But again, that's a small patient population. 
So that's the way most of us are dividing this down. 
Genetic abnormalities giving rise to ovarian cancer-- BRCA1, BRCA2-- will get PARP inhibitor maintenance. 
And if they don't, they should be offered bevacizumab. 
What's the next step? And would there be an option to give both? The answer is, absolutely. 
So there are several ongoing trials looking at the combination of olaparib with bevacizumab, so we'll know the answer to that. 
If I were to give an educated guess, I would say we'll be treating with both agents in the near future.