Q and A Session

Moderator: Good afternoon, and thank you for joining us for today’s teleconference. My name is Kristin Dickie, I am with Princeton Media Associates, and I will be your moderator for today’s Q and A session.  Joining us today are Dr. Ruth O’Regan, Dr. Jeannine McCune, and Dawn Holcombe. Dr. O’Regan, do you have any opening comments?

Dr. Ruth O’Regan: I would just to thank everybody for joining us for this very important topic.

Moderator: Thank you. Dr. McCune, do you have any opening remarks?

Dr. Jeannine McCune: I would also like to thank everyone for participating in this activity and to welcome questions regarding this important issue.

Moderator: Thank you. Ms. Holcombe do you have any opening comments?

Ms. Holcombe: Just very briefly, that as we are looking at further defining diagnosis and management and we are tailoring measurements like HER2, it is going to become far more important for us, in order to be able to use these drugs, because we are going to have to prove that we have the right marker and have indicated the right drug. And, if anyone has questions or concerns about that—one of the most important takeaways is that we are now starting not only to try to identify what the right treatments are but we are in the realm of being able to identify markers that will help us prove the value of each treatment for each patient.

Moderator: Thank you. Our first question today comes from our planning committee. How have targeted therapies changed the management of HER2-positive breast cancer?  Dr. O’Regan, would you like to comment?

Dr. O’Regan:  Well, I think the first thing to point out here is—as you saw on the slides—these HER2 positive cancers really have a very poor outcome. They run a very aggressive course with a very high recurrence rate over the first 2 to 3 years after diagnosis. By using HER2-directed therapy, particularly trastuzumab, but also lapatinib, we have been able to change the natural biology of these cancers. So, in fact if you look at the data from the adjuvant studies what you are finding now is that there is a 50% decrease in the recurrence rate in patients who received trastuzumab-based chemotherapy versus not. So, essentially what you have really done for these patients is taken what I think is really a poor prognostic cancer and hopefully turned it into actually a reasonably good prognostic breast cancer.

Moderator: Thank you. Dr. McCune, do you have any thoughts on this topic?

Dr. McCune: Yes, in addition to the clinical benefit that Dr. O’Regan has mentioned for these patients, I think that trastuzumab in its use of HER2/neu-positive breast cancer patients has really helped us in terms of moving oncology from being empiric treatment of cancer patients based on their tumor grade to more targeted treatment based on their tumor characteristics and I think that there are some very important lessons which can be learned about it in terms of how we can improve our delivery of cancer care.

Moderator:  Thank you. Ms. Holcombe would you like to comment?

Ms. Holcombe: Yes, I obviously cannot comment on the clinical, but I do see a there is a tendency on the part of payers to question particularly some of the more costly therapy choices that we are now developing, and they are not questioning whether these therapies are beneficial. They are just questioning to make sure we are giving the right therapies to the right patient. So, as we are moving toward being able to identify HER2 positive, we are going to see more and more payers asking us for the lab value at the same time that we bill for the appropriate treatments so that they can be reassured that we are giving the right drug to the right patients. And, I think that is just one of those hurdles that we are going to need to cross, but it also will make it easier because we will have fewer denials because we are, in fact, justifying that we are using the right drug.

Moderator:  Thank you. Our next question today also comes from our planning committee. Have you had discussion or directive from your private pay insurers or self-administered insurance programs about the use of targeted therapies and the potential effect on payment policy? Ms. Holcombe, would you like to comment?

Ms. Holcombe: Yes, that is actually an extension about what I was just speaking. I think the biggest concern the payers have is that they do not want to see over use or under use of drugs. So, as they are asking for these types of lab values they are trying to prove in their minds and to the patient that they are covering the right choices. We are going to see more and more of these as we develop more markers. I think this is a wonderful first step. We do know that at least 1 payer has already done a study; they believe that they saw significant percentages of inappropriate use and so that is what triggers these types of questions.

Moderator: Thank you. Dr. McCune, would you like to comment?

Dr. McCune: Yes. I agree with Ms. Holcombe that this is going to become more and more of an issue. And, I think really what payers are starting to give more attention to is are the patients receiving these very expensive medications appropriately, and hence, we in oncology need to do better due diligence in terms of clearly defining which patients can truly benefit from targeted therapy, such as trastuzumab.

Moderator: Thank you. Dr. O’Regan, do you have any thoughts on this topic?

Dr. O’Regan: I think unfortunately some of the anticancer agents that we are using now are incredibly expensive and it certainly is a problem. with regard to trastuzumab, it is a little easy because at least you know what you are targeting. I mean, you know if do not have the HER2 receptor that trastuzumab is not going to work. But, when you think about a drug like bevicizumab, which is an androgenic agent, we do not even know what the target for that is right now and that is an incredibly costly drug so I think it behooves us as researchers and medical oncologists to really target the correct population for these novel agents.

Moderator:  Thank you. Our next question today comes from St. Jude Children’s Research Hospital. Please go ahead with your question.

Participant: Two questions, please. Throughout the presentation, I heard a couple of times the phrase, highly statistically significant. I was wondering if you could differentiate between that and regular old, plain old, statistical significance. The second question has to do with the difference between the statistical and clinical significance, especially in some of these abstracts that are showing 3% and 6% differences in survival overall. Thank you.

Moderator: Dr. O’Regan, would you like to comment?

Dr. O’Regan: Well let me just address the second part first of all. I think you bring up a very good point. We are always very excited about these Kaplan-Meyer curves and the differences that we see in them, but really in terms of at least in breast cancer, the effects of adjuvant trastuzumab are actually quite dramatic in terms of survival benefits compared to some of the other agents that we use. So, if you look at the survival benefit is not that great right now, but it is remember at a pretty short follow-up. And, when you look at the disease-free survival curves you are seeing absolute benefits of 10% to 12%, which is really pretty high in terms of breast cancer. For example, if you look at some trials that compared tamoxifen with the aromatase inhibitors, you are seeing like 3% absolute differences in disease-free survival, so really this is pretty marked. The reason that I said highly statistically significant is just really—obviously a P value is a P value—but it is just that I think that some of these P values  were incredibly low in terms of significance and when this data was reported at ASCO for the first time, which I think was about 3 years ago now, the actual P value number was reported on by Eric Winer in his discussion were remarking how markedly significant these curves were, so I think it should really depends on what you treat. For us as breast cancer oncologists, these are very impressive results, but they may not be as impressive if perhaps if you are in some other malignancies.

Moderator: Thank you. Dr. McCune, do you have any thoughts on this topic?

Dr. McCune:  I think the question is very pertinent on 2 points.  It is exactly right how low the p value is does not necessarily speak toward the  statistical significance per se. It is just how unlikely it is that this occurred due to chance that is certainly understand the rationale for that question. And, I think the latter question regarding what is the difference between the statistical importance and the clinical importance is certainly something that as a community oncology is going to have to tackle on a more global, so to speak, perspective because as we get more and more targeted agents we are getting more and more very expensive medications and right now what that is meaning is some patients are going without treatment because they cannot afford it, although it seems like that is a minority of patients now. It is certainly getting into the lay press more and more and more, and I think essentially what we are going to need is more cost effectiveness studies that basically say that for each, whether it be year of life gained or quality of life gained, where are we going to say that it is too much to treat that type of cancer patient. But, I just think that talking about cost effectiveness in oncology is something that has been very politically charged, definitely as long as I have paid attention to it for the past 15 years.  I think that our tides are changing and that we are realizing that we have to take a more global perspective to this instead of having it be individualized patient decisions and I think that question is a very important one.

Moderator:  Thank you. Ms. Holcombe, do you have any thoughts on this topic?

Ms. Holcombe:  Absolutely and I could not agree more with the comments that Dr. McCune just made. I am starting to hear rumblings in the payer world that what is the quid pro quo per dollar of therapy, and our definition of statistically significant results may be subject to a new interpretation. I know that in the workers comp world they have been able to place values on the loss of a hand, an arm, et cetera, even a life, and I am starting to hear a trend towards—and we are not ready to do it yet—but the question is, is there a point, a  demarcation point, where we can say, a dollar of cost is not going to generate enough significant value of return to justify the societal expense of the treatment. And, I do think that this is something we need to watch. I do think this is something we need to be aware of. Many of the research studies that we are traditionally used to doing do not answer these questions. So, it is a whole new way of looking at our world that we need to start to embrace.

Moderator: Thank you. That was our final question for today. 

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