A Leader in Both Research and Practice

Sandra M. Swain, MD

Those who are selected to serve in the prestigious position of president of the American Society of Clinical Oncology (ASCO) are often tasked with making as big an impact in the world of oncology as possible in their 1-year term. But few of ASCO’s past presidents were faced with the multitude of challenges that arose during the presidency of Sandra M. Swain, MD, who is medical director of the Washington Cancer Institute at Medstar Washington Hospital Center and a professor of Medicine at Georgetown University, and is currently ASCO’s immediate past president.

During her term, oncologists felt the impact of a series of budget cuts as a result of sequestration. This came at a time when doctors were also going through the growing pains of changes in the healthcare system as new laws began to take effect. Recently, Swain sat down with Oncology & Biotech News to discuss these challenges and the other pressing issues that will face ASCO in the years to come, as well as her work on the groundbreaking breast cancer drug pertuzumab and the challenges of treating breast cancer patients who are or wish to become pregnant.

OBTN: What was your reaction when the sequester was enacted and what impact have the budget cuts had on cancer care?

Swain: I don’t think anyone thought that the automatic budget cuts, known as sequestration, was really going to happen. I think that’s the shocking thing about it at all. I think the reason Congress even put it in place is because they didn’t think it was going to happen and then this past spring it really did happen. Several things were going through my mind. The first thing was the decrease in NIH funding, which is really affecting the research on many levels.

First of all, with those cuts, you’re not having young researchers being excited and wanting to come into research because they can see all the struggles. That’s really a detriment to having the young creative minds coming into research and involved in the discovery process. Those are the people usually who make the great discoveries when they can be creative, when they’re energetic. That’s really a big problem right there. And then just to decrease funding for things like clinical trials, the clinical trial system, and the cooperative group system is a big problem. It’s already underfunded and we know that many great advances have occurred in clinical oncology with the use of federal funding for clinical trials. For example, Herceptin was approved based on two federally funded clinical trials that put their data together. That has saved many, many thousands of lives and will continue to save more. Without that kind of funding for clinical research we will only be doing trials with the pharmaceutical industry. That’s not necessarily a bad thing. I think we absolutely need to do trials with industry and they have a lot of great drugs. However, we also need to have the flexibility to do those kinds of trials that the pharmaceutical industry is not interested in or may not be related to a specific drug or may involve multidisciplinary therapies. Those are a couple of the concerns for the NIH funding.

Another area that the sequester has affected is the FDA. The FDA has been fabulous in the oncology division in the last several years. The agency has approved more than a dozen drugs for our patients and has really been very progressive in trying to work with the oncology community and approve drugs in a timely way for the high unmet needs of our patients. The agency has also been working long hours to address important drug shortages for oncology and other areas of medical care. Without the funding and with the sequestration cut to the FDA, there’s less money for medical reviews to have drugs approved at an earlier time for our patients and less funding to do the FDA’s important work in monitoring the safety of our nation’s drug and food supply.

The third oncology-related impact the sequester has had is on Medicare. Sequestration reduced Medicare payments by 2%, and it ended up cutting not only the services but reimbursement for oncology drugs. That has hurt a lot of practices because they have to buy the drugs, and then they end up losing money on some of the drugs and they can’t afford to treat the patients.

Moving forward, what needs to be done to address the effects of these budget cuts?

As far as the funding for reimbursement, we at ASCO are continuing to work with our colleagues on the Hill discussing with them how important it is for cancer care because 65% of patients with cancer are Medicare patients. That’s two-thirds of the patients, so it really affects an overall majority of patients with cancer. We are actively talking to our colleagues on the Hill trying to make them aware of the problems with the cuts and working with them to restore funding.

In addition, any planned structural changes in physician payment need to be done in a pilot form. There are a lot of talks now about doing accountable care organizations for physicians if you ask how physicians can change things. But if you know what’s happening and some of the things that have been reported recently, not everyone who was in the original pilot programs is going to continue the accountable care organizations because they can’t afford it. Those pilot programs are essential to be done any time a change is made to look at the lessons to learn to see can you do it, can you not do it, and what are the implications, because a lot of times when you make changes, there are things that happen that you can’t predict.

What are some of the other challenges that ASCO must address moving forward?

There are many other important issues and one of those is how one defines value. There are lots of meetings and talks and all sorts of things about value. So what is value? We spent a large part of this last year looking at that issue and we have a Value of Cancer Care Task Force, previously the Cost of Cancer Care Task Force. We know value is not just about cost. It’s about efficacy, it’s about toxicity, it’s about all the different things that go into different treatments. I think getting to that issue of value is really important.

Along with that, we have a major project called Clinically Meaningful Outcomes. That’s something I really initiated with our Cancer Research Committee. I’ve been doing this a long time and I’ve really felt that in breast cancer recently we’ve made huge advances with some of our HER2-targeted therapies. But for many years, we really had made only incremental advances, and that’s true I think with a lot of the other diseases, too. My feeling, along with Dr. Lee Ellis who chaired ASCO’s Cancer Research Committee when I was president, we both felt strongly that we needed to set the bar higher for efficacy for different treatments. I tasked him and the Cancer Research Committee to come up with what they thought were clinically meaningful outcomes, not statistically significant outcomes,since I think that in clinical trials you can have a statistically significant effect that is not clinically meaningful. They did this and they looked at four different diseases and actually put out a document about 2 or 3 months ago for public discussion and received many comments. Dr. Lee presented the document at ASCO this year and now the group is working on a manuscript. I think this manuscript will be important guidance for oncology researchers, so we can set the bar high to really have the best for our patients. In this group, we’ve also included patient advocates because we feel really strong that we don’t want to just make a little bit of a difference for the patient. We want to make the best difference that we possibly can.

You were involved in the CLEOPATRA trial, which led to the approval of pertuzumab. Now that pertuzumab has been FDA-approved for more than a year, could you describe what it’s like to use this drug clinically and how we might move forward with its use?

Pertuzumab was approved with trastuzumab and docetaxel in June 2012 based on the CLEOPATRA trial and the overall survival data (Figure). It was really outstanding data with an increase in survival that we really hadn’t seen in the treatment of breast cancer. My feeling, having used it a lot and looking at the data, is that it should be used as in the indication—looking at the two drugs together, the trastuzumab and pertuzumab and the chemotherapy. I think that chemotherapy could be paclitaxel. There was a poster presentation at this year’s ASCO meeting looking at pertuzumab and trastuzumab with paclitaxel which showed a very high response rate. I think it was about 50%. So I think the taxane doesn’t matter there. I think for us in the United States that paclitaxel is easier to use, so I would probably use that. I know the NCCN guidelines actually do say taxane. I think that’s one issue. It looks like there’s probably about 8000 to 9000 patients who would be eligible for this treatment in the first-line setting, and maybe in that group, you’d want to say that 4000 to 5000 per year might use it. There are patients who have HER2-positive, ER-positive breast cancer that you may use hormonal therapy and trastuzumab for and not go to the chemotherapy with pertuzumab at that time. I still think it’s a substantial number of patients.

Figure. CLEOPATRA Phase III Trial

P indicates pertuzumab; T, trastuzumab; D, docetaxel

As far as using it beyond first line, there are some studies looking at that, and the study I did at the NCI, which was very small, showed about a 20% response rate with trastuzumab/pertuzumab in heavily pretreated patients. In Jose Baselga’s study, I think most of his patients had not gotten a lot of previous treatment. So there’s not a lot of data out there right now, but I wouldn’t see why it wouldn’t be effective and I know there are studies ongoing now.

In March, as part of my keen interest in clinically meaningful outcomes and trying to get drugs approved more quickly, I worked with the FDA with Patricia Cortazar and Richard Pazdur, and we developed a workshop on looking at the use of surrogate endpoints in neoadjuvant therapy. And we used as an example and had discussion about the different HER2-positive neoadjuvant trials, the NeoALTTO trial and the NeoSPHERE trial, where there were high pathologic complete response rates, and also the NOAH Trial, which showed the outcome was improved when you had a high pathological complete response in HER2-positive patients. Based on that data this workshop really was looking at the draft guidance that the FDA had put out to try to formalize how pathological complete response could be used as a surrogate endpoint. Pertuzumab and trastuzumab will be going in for that indication. I don’t know the details of it, I just know it has been submitted to the FDA for that new indication as a surrogate endpoint.* If the company uses the accelerated approval pathway, of course, subsequent data will be needed to verify that pathologic complete response leads to clinical benefit.

At the 12th International Congress on the Future of Breast Cancer, you discussed breast cancer in patients who are pregnant. Could you tell us a little bit about the challenges faced by this particular patient population?

The reason why I think pregnancy-related breast cancer is important is because it’s clear that women are waiting until an older age to get pregnant now. That has been shown over the last several years. There is an increase in the number of patients who are pregnant and get breast cancer. It’s probably around 4000 to 5000 patients a year in the US who have this, so it’s not an insignificant number. What do you do with them?

Most physicians have only treated maybe one or two of these patients. It’s very scary to have a patient like that. It’s very clear from recent data that Hatem Azim put together where he did basically a case-controlled study of patients who had had breast cancer and then wanted to get pregnant. However, those patients did not have an increased risk of recurrence. I think that’s clear from his study (published this past year in the Journal of Clinical Oncology). It’s the first study that was pretty definitive in patients who had had ER-positive breast cancer, and then they got pregnant and they didn’t have an increased recurrence and their survival was the same. That study supported not getting an abortion if a patient had a pregnancy after breast cancer. The second question is, if a patient has breast cancer during pregnancy, what do you do?

Another recent study that was just published in the Journal of Clinical Oncology was a registry study from several countries in Europe that looked at several hundred women who were pregnant and got breast cancer and compared them to a group of pregnant women who also had breast cancer who didn’t get chemotherapy. The patients who were pregnant got chemotherapy and they did very well compared to the non-pregnant patients. They matched them for age and different treatments and things.

Also, last year in The Lancet, Sibylle Loibl from the German Breast Cancer Group presented their observational study of over 300 patients with breast cancer. I think her paper is very important. It looked critically at issues of whether there were maternal complications, whether there were neonatal complications in patients who got chemotherapy while they were pregnant with breast cancer. What Dr. Loibl’s study showed was that the most important thing was that the patient who was pregnant be allowed to go to at least 37 weeks or longer, because if they delivered before 37 weeks, the babies were smaller and they also had more complications. So they did recommend that they do not try to induce the labor earlier but keep it at 37 weeks. On the other hand, they did not find that there were more congenital malformations in those children who were exposed to chemotherapy. There are several studies in which pregnant women have gotten adriamycin or taxanes and the fetal malformations are not increased in those children. So the recommendation I would have if you have a pregnant patient would be to certainly get a high-risk consult with your OB/GYN, and also to give them usual chemotherapy after the first trimester. What I’ve done is usually used AC but you certainly can use taxanes, and more and more data are coming out showing that that’s probably very safe.

^*Subsequent to our interview with Dr Swain, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 13-0 with one abstention to recommend approving combination therapy with pertuzumab, trastuzumab, and docetaxel for the neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer.