Current Issues in Gynecologic Oncology: A Discussion With John Curtin, MD

John Curtin, MD

Many contemporary issues in the US healthcare system affect clinicians in all areas of medicine: The Supreme Court hearing on the constitutionality of certain aspects of the Affordable Care Act, the development and makeup of accountable care organizations, and relationships with industry. Other issues, such as the current shortages of oncologic drugs, affect oncology specialists to a greater extent than they do other clinicians.

Some issues are even more specific to the field of gynecologic oncology, such as finding ways to improve survival and cure more patients with ovarian cancer, eradication of cervical cancer, and encouraging cooperation with other clinicians–including nonphysicians– who have a special interest in gynecologic cancers.

At the 2012 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer, held in March in Austin, Texas, outgoing SGO president John Curtin, MD, director of Gynecologic Oncology, New York University Langone Medical Center in New York City, addressed all of the above-mentioned issues and more in a wide-ranging interview with Oncology & Biotech News.

OBTN: Shortages of oncologic drugs have made a lot of headlines recently. How have the shortages affected the field of gynecologic oncology?

Dr. Curtin: For our patients and for the members of SGO, the primary problem remains the availability of Doxil (liposomal doxorubicin). Our society has been taking a proactive approach to this problem, discussing the shortage with the manufacturer. Additionally, we have taken an interest in the fact that the FDA has allowed temporary importation of Lipodox, which apparently is an agent that has been around for awhile, but the manufacturer never sought generic equivalency. The FDA felt it needed to allow this agent to come into the country, given that it doesn’t look like there is going to be any Doxil available for awhile.

We know that ovarian cancer patients aren’t the only patients who benefit from Doxil. I believe it is approved for multiple myeloma in combination with another agent. It is approved for Kaposi’s sarcoma. But it seems like it is a primary drug for ovarian cancer. I have seen estimates that 7000 women a year are being treated with Doxil.

The shortage of Doxil is a little different from shortages of other drugs, in that some of those generic drugs are in short supply because there isn’t a big interest among pharmaceutical manufacturers to make them, because there is such a close margin between cost and revenue on them. With Doxil, the company that had licensed it contracted with another manufacturing plant for production. That plant had sort of a poor infrastructure, and it didn’t seem like they were keeping up. Finally, the situation got to the point that the FDA gave them a very critical review, and, according to my understanding, the manufacturing plant voluntarily shut down before the FDA could close it. I have read the FDA report, and the issues with the plant were related to manufacturing processes, quality control–a lot of it was about just good manufacturing practice.

The toughest thing for physicians has been trying to explain to patients why this very active drug–which is relatively easy to give to patients, who have a relatively good quality of life while on it, and that works in a substantial proportion of patients–all of a sudden is not available. It became unavailable in July 2011, and we keep hearing different timelines for when it’s going to come back.

Physicians who might not be familiar with this issue might look at it and say, “What’s special about liposomal doxorubicin? Why can’t you just use the old Adriamycin or one of its generics?”

The big difference is toxicity. Having treated patients with doxorubicin in the past, I know the biggest problem is that you’re limited to about eight cycles, and then you start to get unacceptably high rates of cardiac toxicity. When you give doxorubicin, you have to be very careful because it’s a desiccant and can cause tissue injury. A lot of patients require central lines. With liposomal doxorubicin, you avoid a lot of that. There are still some patients who develop cardiac toxicity, but the number is very low. Most patients tolerate the drug quite well. It does seem to be something about the formulation. By putting the doxorubicin into liposomes–and there are a lot of theories about why it works–it appears to deliver a higher concentration of doxorubicin to the tumor and minimize the toxicity to normal tissue, which is an ideal way to target a drug like doxorubicin.

Have you heard when production of liposomal doxorubicin might resume in the United States?

I’ve heard two things. I’ve heard that production will start up again in July 2012, and I’ve heard that it will resume at the end of 2012. The problem is that we have heard several different timelines that have passed, and there’s no drug produced, so it’s frustrating, and I no longer expect the dates that I hear to be accurate.

How are gynecologic oncologists dealing with the absence of this frequently used drug?

There are drugs that are approximately equivalent in terms of response. Single-agent topotecan compared favorably with liposomal doxorubicin when they were compared in a head-to-head study. The difference is that topotecan is given by a 4-day infusion. The patient has to come in on 4 consecutive days for an intravenous infusion, every 3 or 4 weeks. For a lot of patients, that is a heavy burden, particularly if they have to travel a long way. The toxicity profile is a little different, mostly related to decreased white blood cell count and decreased platelets. That can be cumulative, so with each cycle of topotecan, there is a little bit higher incidence of toxicity. With respect to combination therapy, a study about 3 years ago showed that the combination of carboplatin and liposomal doxorubicin in platinum-sensitive ovarian cancer was superior to carboplatin and paclitaxel, which had been sort of the standard for platinumsensitive patients. In a lot of cases, I think we are probably treating patients with carboplatin and paclitaxel again, giving up a little bit of effectiveness because we don’t have the drug that works the best.

Moving on to other issues, the SGO business meeting this year included a discussion about the organization’s relationship with industry and how that relationship is changing. Please elaborate on this topic.

It’s not just an SGO issue. Every national medical society is facing a shift in how they fund their education function. It’s driven partly by regulation and partly by our own internal desire not to have any obvious, or any appearance of, conflict of interest. As the regulations move forward, it’s going to be harder to justify getting pharmaceutical money to support continuing medical education. We are compliant with all of the accreditation bodies, but I think, at a federal regulatory level, people want to know there is no conflict of interest when pharmaceutical companies give money to support educational programs. On the other hand, pharmaceutical companies are facing increasing budgetary concerns, and they are not able to fund as much as in the past. We are faced with a situation where we used to be able to fund a lot of our meeting with educational grants, and those monies are disappearing. We feel that the annual meeting has great value. It’s a great place to exchange ideas. It’s a great place to present new data. We just have to find a new way to fund it.

The economics of healthcare have been at the forefront again as a result of the Supreme Court’s decision to hear arguments about the constitutionality of certain aspects of the Affordable Care Act. What are some of the concerns that your organization has regarding the current economic status of medicine?

Well, I think some of our concerns sort of mirror the concerns that healthcare practitioners in general have. What’s the sustainability of Medicare, moving forward? Will Congress eventually address the Sustainable Growth Rate legislation? They tend to keep passing the buck. They pass a 1-year patch, and then it gets to the point that ultimately they have to make a decision on that one way or the other.

The healthcare bill just has so many provisions in it. There are a couple of areas that we are a little concerned about, such as the accountable care organizations and the provisions for them. We are a little concerned that women with gynecologic cancers might not be cared for by specialists who do that as the primary focus of their clinical practice. Our society changed its name from the Society of Gynecologic Oncologists to the Society of Gynecologic Oncology to reflect the fact that you don’t have to be a gynecologic oncologist to take care of a patient with ovarian cancer or endometrial cancer, but you have to be a specialist–either gynecologic oncologist, medical oncologist, radiation oncologist–whose primary focus is on patients with gynecologic cancers. We believe strongly that patients are best served when the person who takes care of those cancers is someone who has the expertise to know what is going on and how best to care for it.

When you start looking at things like accountable care organizations, we want to make sure we have a place at the table when those physician panels are constructed. It’s a little reminiscent of when the HMO process came into being. There were some very restrictive HMOs that didn’t include gynecologic oncologists. We fought that battle 20 or 25 years ago, and we just want to make sure we don’t have to fight it again.

With regard to other provisions of the healthcare act, obviously if you had more patients with coverage, we might see some of the benefits of things like access to screening, particularly in terms of things like cervical cancer. Cervical cancer is a great success story for the vast majority of the population in the United States and in most developed countries. However, in the United States, underserved and uninsured patients who don’t go for screening still account for a big percentage of the patients with invasive cervical cancer. Could you hope that if you had broader insurance coverage that those patients would come in and take advantage of screening, since it is now covered? You would hope so, and that ultimately you would see a decline in cervical cancer. Maybe– by combining screening and the human papillomavirus (HPV) vaccine–in 5, 10, or 15 years, you could see another significant decrease in cervical cancer like we’ve seen over the last 40 or 50 years.

SGO has been at the forefront of a lot of issues surrounding HPV vaccination. What observations do you have about the current status of vaccine uptake?

We’re in a little unusual situation, in that the patients we care for are not typically the patients who would be vaccinated. We care for the patients who already have a precancerous condition or invasive cancer. The key issue with vaccination is getting the message out about the importance of reducing this cancer to pediatricians, general OB/GYN practitioners, and family practitioners, and letting them know that they should be vaccinating patients.

Human papillomavirus (HPV)

A speaker at one of the plenary sessions said HPV vaccination should be routinely offered to adolescent boys. Your thoughts?

It’s a basic public health concept that if you vaccinate the part of the population that is the so-called “vector,” then you should eliminate the disease. So, I wouldn’t disagree with [the speaker] in that if you vaccinated every boy or young man and it was 100% effective, you would eradicate HPV diseases in women, as well. My children don’t like me to make it personal, but I do have a daughter who has been vaccinated. She knows that I mention it, and, now that she’s a little older, she doesn’t have a problem with it. I certainly would have my son vaccinated, as well.

What do members of your organization consider as major advances in the management of gynecologic cancers?

In the diseases we care for, we have seen tremendous change in the management of some of the conditions. Ovarian cancer is an example. First, I would emphasize that we have a long way to go. However, for a condition that often presents in advanced stages, we have achieved, for a substantial proportion of patients, long responses to therapy where patients can return to a lot of their normal activities. We have incrementally improved the survival of those patients. Having been doing this for a long time, I think we don’t look for the big home run, but incremental improvements along the way. We have a much better understanding of endometrial cancer in terms of the idea that we can minimize the amount of surgery for some patients. We can eliminate lymph node dissections for some patients. Certainly, the introduction of minimally invasive surgical techniques has had a major impact on endometrial cancer. With respect to cervical cancer, I think the advances occurred 10 or 15 years ago, with the establishment that the combination of chemotherapy and radiation therapy made a significant improvement in response rates and overall survival.

One of the new things we are seeing in all of the cancers is the importance of at least considering fertility preservation for younger women diagnosed with gynecologic cancers. I know that applies to all cancers, but particularly to our field. That used to be unusual throughout the field of oncology, but now I think that discussion has become part of the routine evaluation. We have heard more discussions about that at this meeting.

Do you see any other advances on the horizon, some that perhaps were discussed at this meeting?

We all hold out hope that the targeted agents that are being brought to clinical use have some promise to supplement, or even replace, some cytotoxic chemotherapy, which is usually associated with a lot of side effects. Ultimately, treating patients with cytotoxic chemotherapy will cure some patients, but others will not be cured. We heard some reports at this meeting about combining bevacizumab with upfront chemotherapy, including an update of the OCEANS study. We heard more information about the use of PARP inhibitors. Certainly, there are other agents that are being discussed. We’re learning more and more about tumors’ genetic signatures and how to identify tumors and classify and define them, and potentially help us make decisions about which agents to use and how to use them most effectively by using information about individual tumors.

What is the health of your organization and specialty?

The name change for the society is just one small part of our realignment as we move forward. We have expanded our membership, which used to be limited to gynecologic oncologists. We recognized we were excluding some talented physicians who felt just as passionately as we did about taking care of patients and improving outcomes for patients with gynecologic cancers. We have grown our membership by about 20% in the last 2 years. A lot of that growth has included medical oncologists, radiation oncologists, as well as allied health professionals, such as nurse practitioners and physician assistants. We now offer continuing education credits for nurses as well as physicians. We want nurse practitioners to come here and not just take part in our education. We have sessions that are being led by nurse practitioners. It just expands our learning and educational offerings.

In the past 10 years we have seen significant growth in the number of fellowship programs, from the low 30s to about 45. The number of applicants for the 50 or so fellowship positions every year is 70 to 80, so about 60% of people who apply get a fellowship spot. There are no fellowship spots that go unfilled. That’s not true of all specialties.

As we expand our own membership, we are looking to partner with other organizations. We are very happy to work with larger organizations, such as ASCO and ACOG. Another area of interest is international collaboration, not just on educational and scientific meetings. A substantial number of SGO members are interested in volunteer opportunities overseas in underserved areas. We’re working with Health Volunteers Overseas, and we have placed quite a few members, who travel to underserved areas and bring their expertise to work toward the goal of raising the standard of care. A lot of our members feel very passionate about that. We realize that we live in a resource-rich society, and we should find ways to give back.