Q: Tell me about the trial you're involved in.
Audeh: We were involved in the first phase II trials, and we are now moving into larger phase II trials, which, depending on those results, would then lead certainly to phase III trials comparing this drug against the standard chemotherapy drugs that most women are forced to use currently.
Q: What are you seeing so far?
Audeh: We have seen long-lasting responses, and in some cases, actual remissions where there is no identifiable cancer anywhere; and the astonishing thing is not only that THIS happened with a simple pill, but that it has lasted so long. Some of these women have been in remission for over a year, something that would be extremely unlikely with any available chemotherapy for ovarian cancer.
Q: What is this drug doing for people?
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Cancer development
William Audeh, M.D., shares more about what he calls the most exciting development in cancer therapy.
 
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Audeh: It's called A PARP inhibitor. It's inhibiting an enzyme called PARP, which is involved in repairing DNA damage. It's exploiting the weakness in these cancers because by having mutations in the BRCA gene, they are already somewhat deficient in their ability to repair DNA damage; and this drug simply adds on additional damage without the kind of toxicity that chemotherapy normally produces. Under those circumstances, the cancer cells appear to be extremely sensitive without harming the normal cells in the body.
Q: Has this drug only been used on patients with that certain genetic defect?
Audeh: In the phase II trials, yes, this drug so far has only been given to women with ovarian cancer and breast cancer who are found to have a mutation in one of the BRCA genes -- BRCA 1 or 2; and women who are born with a mutation in those genes have a much higher likelihood of developing breast or ovarian cancer. Fortunately, for this drug, the cancers that develop in these women seem to be exquisitely sensitive to the PARP inhibitor. This is an example, I think, of the most exciting development in cancer therapy, which is targeting treatments specifically to the patient’s genetic makeup, especially in a way that only harms cancer cells and leaves the normal cells alone; and I am sure that this is just the beginning of a long list of targeted therapies that will do the same thing.
Q: Does this trial jump start a whole branch of research into targeting genetic defects to treat cancer?
Audeh: Exactly. Once we have proved the concept, as I think this trial has, than you can take the science from the laboratory and apply it to the clinic and have an exciting outcome like this. It really encourages us to do the same thing, perhaps in other cancers that have different kinds of DNA damage defects -- for example, with this drug -- but the concept is being applied to many cancers with many other drugs, because science has made great strides in unraveling the workings of most cancers. We really do know a lot about the molecular defects at the basis of these cancers, and we have many, many drugs that we know will target those defects. It is just a matter of getting the right drug TO the right patient.
Q: What is the benefit of not having to undergo chemotherapy?
Audeh: The benefit I have seen has been enormous, primarily with quality of life. Many of the women that we treated in this trial were very active women before their disease; they were working, they had active family requirements they were not really able to keep up with because of the effects of chemotherapy. For the women who responded to this drug and were on it month after month and felt better and better, several of them went back to work. They are doing things that they could not do before because they have their energy back, and it does not cause the kind of physical changes that chemotherapy often causes such as hair loss, loss of appetite, susceptibility to infections when they are [undergoing] chemotherapy. None of that is the case with a drug like this.
Q: Do you think this kind of treatment attacks the root of the cancer as well as the symptoms?
Audeh: Absolutely. Although many people have been helped by chemotherapy, and many have been cured by it, it ultimately is not the best way to deal with a disease like cancer. As we get closer and closer to knowing the molecular basis of cancer and we have more refined drugs such as this one that goes right after the specific problem, we can avoid the collateral damage that non-specific therapies like chemotherapy have always produced.
Q: Do you think one day we could eliminate chemotherapy as a cancer treatment?
Audeh: I sure hope so. I think that the trend now with not just this drug -- many, many other targeted therapies -- is certainly in that direction. I have had several full clinic days, for example, where I did not see a single patient on chemotherapy. Every one of them was on some kind of targeted therapy -- either standard, currently available therapy or experimental drugs such as this one. So I do not think what you are describing is that far away.
Q: How common are the BRCA I and II genetic defects?
Audeh: It is the cause of about five to 10 percent of breast cancers, and it is thought to the cause of about 10 percent of ovarian cancers. These particular genes certainly do not explain the majority of cancers that develop of this type, but we do think that many of those other cancers still have defects in genes that would make them susceptible to this drug; and we are currently in the process of trying to identify which other genes might identify sensitive women so that we can apply a drug like this more broadly, and ideally perhaps in combination with other equally nontoxic drugs where you are really targeting more than one aspect of the cancer.
Q: Are there any side effects or risks to this drug?
Audeh: That is part of the clinical trial, of course, to monitor these women very closely to look for any side effects or risks, and so far we have seen very little -- certainly, nothing of the type that we would see with chemotherapy drugs. Some people have had some fatigue initially, but that has really been most of the problems. Most people from Barbara’s case feel perfectly well.
Q: How exciting is it to be on the cusp of something huge here?
Audeh: It's tremendously exciting, in part because, for many years, I have been taking care of women with these mutations -- with BRCA I and II mutations -- because they have a higher risk of breast and ovarian cancer. I have been waiting for a drug that would take advantage of that genetic defect in a much more targeted way. So when this first became available, we were at the front of the line wanting to be part of the trials. In fact, we were one of the first in the world to be able to use these drugs in this setting. It's tremendously satisfying, especially when you see the science start from the laboratory and move into the clinic to the point where you are actually changing people’s lives -- making them feel better and helping them get back to normal.
Q: Where do we go from here?
Audeh: For this specific drug, it is being used in a number of other cancers where we also think there is an underlying genetic defect that may make them more sensitive. In some cases, it still requires combining this with certain chemotherapy drugs that may enhance the effect of both; but certainly in ovarian cancer -- where this drug has shown a great deal of promise -- it is expanding now into a much larger phase II trial, which, if it turns out the way the earlier trials did, will lead to a phase III trial and, one hopes, FDA approval; so this drug can be available to any doctor with a prescription pad.
Q: Is there any estimation of how long it will be until it is approved by the FDA?
Audeh: My hope would be two or three years. I think the urgent need for new cancer therapies is on everyone’s mind, and everyone hopes that the FDA is going to allow these drugs to be widely available as soon as they have proven they are safe and effective; and I am very hopeful that it will be the case with this drug.
Q: Do you think it's a possibility that this drug could manage cancer like a chronic disease?
Audeh: That is really the outcome of using this -- targeted therapies, even when we cannot completely eradicate every last cancer cell; knowing what makes the cancer cell tick and then applying a drug like this is able to slow it down or stop it so that cancer becomes a chronic disease that people simply manage and live with, just like any other that requires medication from time to time, but it's still something that does not interfere with a person’s daily life; and I think we are getting there with many cancers using this kind of approach.
