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Our Ask Me Anything (AMA) with Dr. Melissa Frey is starting now.
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Hello and thank you everyone for joining us today for our Ask a GYN-ONC Anything. And special thanks to Dr. Frey for participating. Dr. Frey please tell us about yourself.
Currently there are 3 FDA approved PARP inhibitors.
Olaparib
Rucaparib
Niraparib
There are differences in the FDA indication for use (maintenance after frontline treatment, maintenance after recurrent disease, treatment). There are also differences in the side effect profile.
The current FDA indications for PARP inhibitors are as follows:
1. Women with BRCA1/2 mutations following front line treatment as maintenance therapy - Olaparib
2. Women with platinum-sensitive relapsed disease (the ovarian cancer recurred and the woman had a complete or partial response to treatment) as maintenance therapy - olaparib, rucaparib, niraparib
3. Women with recurrent disease and BRCA1/2 mutations as treatment - Olaparib and Rucaparib (germline or tumor BRCA mutations)
This question is from someone on our online community. Has there been any progress with vaccines to prevent Ovarian Cancer. I am an Ovarian Cancer survivor and I am concerned about the possibility of a recurrence.
Maintenance therapy is treatment for women who have had a complete or partial response to treatment. The goal is to find treatments with good tolerability and limited side effects, that women can remain on for long periods of time. The concept is to delay the time to recurrence or progression.
In general the concept is to remain on therapy until the disease progresses/grows or the drug becomes intolerable (side effects). However this is an area under investigation and we will likely learn more from ongoing and maturing clinical trials over the next few years.
Currently olaparib is FDA approved for women with germline or somatic (tumor) BRCA1/2 mutations.
Some physicians in the US and more so in Europe are using Bevacizumab.
The decision about whether or not to be on a maintenance therapy is complex and requires a detailed discussion between the patient and treating physician. All drugs have common mild side effects and all drugs carry risks for serious side effects. These risks must be carefully weighed against the potential benefit.
This depends on the specifics of the clinical scenario.
For women who have been in remission for a long period of time then a biopsy is often indicated. In my practice, I generally obtain a biopsy at the time of first recurrence. However in women who have experienced multiple recurrences and who have had a short interval since the prior recurrence a biopsy is not always necessary.
If there is any question as to whether or not a liver lesion could be something else (not ovarian cancer, for example a non-cancerous cyst or a second primary cancer like a new liver cancer) then a biopsy is helpful and important. However, if based on the clinical picture it is clear that the liver lesion is recurrent ovarian cancer then a biopsy is not always necessary.
Each procedure comes with risks and benefits, which need to be discussed. A woman should talk to her physician about the pros/cons of a biopsy and how the information obtained from the biopsy will guide treatment decisions.
Currently there are no guidelines to direct when tumor testing or tumor profiling is completed.
In the past tumor testing was often performed at the time of ovarian cancer recurrence.
However, the recent FDA approval of olaparib may change our practice.
Specifically the new approval states that women with a germline or somatic BRCA mutation can have treatment with olaparib following a partial or complete response to first-line platinum-based chemotherapy.
This means that women with tumor BRCA mutations may select a PARP inhibitor as a maintenance following treatment.
Germline mutations in BRCA (those inherited from parents) are found with blood tests for mutations. However the somatic mutations require tumor profiling.
In my practice I now discuss and offer tumor profiling and germline testing at the time of diagnosis to help guide individualized patient care.
Based on the guidelines from many medical societies including the Society of Gynecologic Oncology (SGO) all women with ovarian cancer should have germline genetic testing. This testing is a blood test that can identify genetic mutations that increase the risk for developing ovarian cancer. Identifying a mutation has many important implications - treatment, prognosis, risk of other cancers (e.g. breast for BRCA mutations), and risk for family members (first degree relatives will have a 50% risk of sharing the same genetic mutation).
All patients should have the opportunity to have genetic counseling and testing. This can be offered by a gynecologic oncologist or a genetics team.
We know less about the implications of tumor profiling. However with the approval of new drugs based on tumor profiling results, many physicians are now incorporating tumor testing for women with ovarian cancer.
Another issue - what genes should be included in genetic tests for women with ovarian cancer?
In the past, ovarian cancer genetic testing often included only the BRCA1/2 genes.
However, we now know that many other genes can contribute to ovarian cancer (e.g. Lynch syndrome genes, RAD51C, RAD51D, BRIP1). And this list will likely grow as genetic testing uptake increases and genetics research advances.
The complexity of genetic testing and the constantly changing medical understanding of this area highlight the importance of genetic counseling prior to genetic testing.
Women should have the opportunity to discuss their personal and family history in the context of available tests and the implications of tests.
Several of the questions I have are related to things people ask me. For example:
•Once I get to a remission, how often should I be seeing my oncologist and what tests should I expect? I hear some people see their oncologist every 2-3 months and in addition they get both a CA125 and a CT Scan. My doctor doesn’t want me to have a CT Scan. Is that normal?
Regarding CA125 and CT scans - this is a more complicated issue. If a woman has a suspected recurrence (for example if she has new symptoms or an abnormal finding on an exam) then CT scan and CA125 can be important.
For women without symptoms there are pros/cons to routinely checking CT scans and CA125 and therefore the decision must be made after a discussion with the treating physician.
Second opinions can be extremely helpful and important.
A woman needs to have complete confidence in and comfort with her treating physician and if there is ever an question/concern meeting with another physician / second opinion is important.
The physician also wants to have patients who feel confident and comfortable with her care and should support second opinions. Often the second opinion reconfirms the treatment plan provided by the primary physician and can offer the patient added confidence with her care.
This testing is available and many physicians use information to help guide treatment decisions when there are multiple options available to a patient without a clear best choice.
However, further research is needed to determine the true efficacy and utility of this type of tumor testing as a method to direct treatment for ovarian cancer.
Chemotherapy-induced neuropathy remains a major issue for women with ovarian cancer undergoing treatment. Many of the commonly used drugs that are effective in treating ovarian cancer can result in neuropathy.
As chemotherapy-induced neuropathy can cause severe motor and sensory symptoms it is critical that women discuss any nerve-related issues with their physician. This discussion should occur prior to each treatment and women should be aware of early warning signs so that they can report them.
When a neuropathy has developed there are medical treatments available that can be prescribed by the gynecologic oncologist, there are also drugs that can be interchanged where the effectiveness in treating cancer is similar but the risk of neuropathy is significantly lower.
The cells from the ovary or fallopian tube that made up the original cancer can recur or reappear in other areas. Most commonly this is in the abdominal/peritoneal cavity but can also be more distant (e.g. liver, lungs).
Thank you for your time Dr. Frey! And thanks to everyone who submitted questions. Stay tuned for future editions Ask a Gyn-Onc Anything. We will be holding three of these sessions in 2019!
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