Ask the Expert

Ask the Expert

Questions following the 8/14/18 webinar, “Breaking News In Breast And Ovarian Cancer And What Should I Make Of It?”

Q1:  Is the thought from platinum-resistant ovarian cancer that, even if I am without evidence of disease from being on the PARP inhibitor Rubraca, do I still have cancer? Does it ever go away completely, or is there not enough known about fallopian tube/ovarian cancer?

Dr. Sharyn Lewin: It’s a tough question to answer. No evidence of disease means that we don’t have a way to detect any cancer by any clinical measures. We don’t see it on a CAT scan, PET scan or any imaging, and we don’t see it in an elevated blood marker like a CA 125. Does it ever go away completely? One of the frustrating things about ovarian cancer is that, for the majority of women, we can often get them into a clinical remission where we don’t have any evidence of disease. But, for the majority of women, they do experience a recurrence. And when that recurrence happens, women are often treated again with chemotherapy, sometimes with surgery followed with chemotherapy, and the PARPs are often used as maintenance. Ovarian cancer becomes more like managing a chronic disease, where women can be on and off chemotherapy for many years.

One of the things that is quite frustrating is, why do women recur when we really don’t have any evidence of disease? That is something that researchers are working on to try to find answers. The PARP inhibitors and all the data on maintenance therapy for PARP inhibitors is to extend the amount of time that women remain in a clinical remission. That data has been very promising. For a woman with platinum-resistant ovarian cancer to be in a clinical remission is really excellent, and the hope is that she will be in a remission for as long a time as possible.

Q2: What is the longest someone has been on a PARP inhibitor for ovarian cancer safely, with efficacy?

Dr. Sharyn Lewin: The original PARP inhibitors that were FDA approved were for women that had treatment of disease that had at least three prior lines of therapy, but also had a germline BRCA mutation; although, there were women treated with PARP inhibitors on a clinical trial prior to that FDA approval. There are some women who have been on the drug for four or six years, if not longer. All of the data supports that women stay on the PARP inhibitor as long as it continues to be effective and as long as they’re not having significant toxicity.

The longest in my own experience has been about four or six years. But I’m sure there are women that have been on longer, depending on if they were part of clinical trials where they had access to the drug initially.

Q3: What are the conditions when a patient would need to stop taking a PARP inhibitor for ovarian cancer?

Dr. Sharyn Lewin: If a woman’s cancer progresses while she’s on a PARP inhibitor, or if there is some type of unacceptable level of toxicity, then we would stop the PARPs. Initially, when a woman is on a PARP inhibitor, we see most of the toxicities within the first two to three months. We often manage that by holding the dose and then letting the toxicities resolve, and then sometimes a dose reduction. Usually, the toxicities can be managed because those often happen within the first two to three months while they’re on therapy. But we would stop the PARPs if for some reason we’re not able to manage the toxicities, but that’s very rare.

Q4: For someone with a BRCA mutation who has a family history of breast and ovarian cancer, would a PARP inhibitor be useful in preventing ovarian cancer?

Dr. Sharyn Lewin: There is no literature yet on using PARPs to prevent cancer. It’s a great question. For someone who has never had a cancer diagnosis, a better choice is something that’s data-driven. For example, if we know someone with a BRCA mutation has a family history of breast and ovarian cancer, we would certainly want that person to have genetic testing and counseling. Even if he or she does not have a mutation, we might still want to treat them like a high-risk patient, with either increased surveillance or even prophylactic surgery. Those options would be better than giving a PARP inhibitor, just because we don’t have any data on PARP inhibitors preventing cancers in someone that doesn’t have a personal history of cancer.

For example, even if someone is BRCA negative but has a strong family history of breast and ovarian cancer and is high-risk enough, we may recommend mammograms alternating with breast MRIs every six months to increase surveillance. For ovarian cancer, when women are done having children, we may recommend removing the tubes and ovaries as a prophylactic measure. But certainly, those people with family history of breast and ovarian cancer should have genetic counseling and testing because it helps us accurately stratify their risk and determine their treatment recommendations.

Q5: For someone who is BRCA1 positive with a family history of primary peritoneal cancer, is there any additional screening that would be recommended after TAH-BSO outside of mammogram and breast MRI?

Dr. Sharyn Lewin: Right now, the data does not support any additional screening for primary peritoneal cancer once someone has had removal of the uterus, cervix tubes and ovaries. The risk of primary peritoneal cancer, even if someone has a BRCA mutation, is about 2% or less for the general population risk. We don’t feel that having a BRCA mutation puts people at increased risk of primary peritoneal cancer. So right now, there isn’t any additional screening that would be recommended.  Of course women should have their appropriate breast screening and see their gynecologist once a year for a pelvic exam. But other than that, there isn’t any additional screening that would be recommended.

Q6: Is there any data for use of PARP inhibitor in BRCA2 positive women with recurrent ovarian cancer if one has already failed a different agent? For example, olaparib after failing with rucaparib.

Dr. Sharyn Lewin: PARP inhibitors are new in the maintenance arena and treatment arena. There will be data emerging about having one PARP after another PARP – for example, someone who fails one PARP inhibitor, and then they go on to chemotherapy, and then re-treatment with another PARP inhibitor. That data is going to be coming out, hopefully, this year.

In the absence of any data, as long as that patient is still partially platinum-sensitive, I definitely would try a different PARP.  And there is some thought that maybe olaparib might be the best one of all the PARPs on the market for those that have a BRCA2 mutation. But, the real key is, as long as these women with recurrent ovarian cancer are still at least partially platinum-sensitive, they definitely can have a different PARP inhibitor.

Q7: Do you know how far away we are for a cure for ovarian cancer?

Dr. Sharyn Lewin: I would love to see a cure for ovarian cancer, as well as many other types of cancers. It’s difficult because it’s not a very common cancer, since there are only about 22 thousand women every year in the United States diagnosed. It’s not as common as some of the other cancers, even though it is so difficult to catch in the early stages, and difficult to treat when it recurs. Researchers are working on ways to have better screening, to find cures, and to prolong or prevent any recurrences. I encourage everyone to keep supporting research and clinical trials because that’s how we advance the science to get closer to that finding a cure.  I hope one day I can say that we can find a cure for this disease.

Q8: What do you think about the possibility of a cancer vaccine?

Dr. Sharyn Lewin: Immunotherapy and vaccine therapies are something that’s been an interesting area of research. It would be tough to have one cancer vaccine that would treat all cancers, but cancer vaccines that could help prevent or treat other cancers is a really intriguing idea. I, unfortunately, don’t think we’re anywhere near that yet, but hopefully the science will continue to evolve where we could get close to that.

There are certainly some cancers that we can prevent. It’s an important time to also remember lifestyle issues. There has been data saying about half of all cancers in the US, which is a huge number, could be prevented if people had lifestyle modifications. For example, if they ate a healthy diet, they didn’t smoke, they used alcohol in moderation, they exercised 150 minutes a week, which is 30 minutes, five times a week, and if they stayed within an ideal body weight.

There’s a huge link with obesity and endometrial cancer, ovarian cancer, breast cancer, colon cancer. Many of the top cancers that we see are linked, now, to obesity. Lifestyle issues are very, very important, and I think it’s easy to forget those things.

Q9:  For someone who is KRAS-variant, would the treatment be different, if at all?

Dr. Sharyn Lewin: The initial treatment for ovarian cancer when someone is initially diagnosed is always a combination of surgery and chemotherapy. Hopefully, it’s surgery first to remove all residual disease, followed by chemotherapy. That would stay the same, regardless of any type of genetic mutation. Although, we do know that women with BRCA mutations may do better from intraperitoneal chemotherapy.

We know that a KRAS variant is inherited. It’s a germline mutation like BRCA1 and BRCA2 mutations, and it can serve as a genetic marker for an increased risk for ovarian cancer. If it’s found, other family members should definitely be tested and undergo prophylactic surgery. But even though it could be a new genetic marker for ovarian cancer risk, to my knowledge, we haven’t found any targets yet that help with ovarian cancer treatment. So far, the treatment would be pretty standard in terms of surgery and chemotherapy.  It would potentially be followed by a clinical trial, and if a recurrence happens, maybe second-line platinum-based therapy and then a PARP inhibitor.

To my knowledge, there isn’t a targeted therapy yet with ovarian cancer for people that may have a KRAS variant. It’s something that’s definitely been utilized in colon cancer, but to my knowledge, we don’t yet have a targeted drug that would be useful in ovarian cancer.


If you have any personal questions or concerns, contact Sharsheret’s clinical team at [email protected]