IGCS 2010, 23-26 October, Prague

Key messages from IGCS 2010

Dr Richard Barakat – Memorial Sloan-Kettering Cancer Center, New York, USA

Dr Richard Barakat, it’s great to have you here. Thanks for making the journey to Prague which, of course, is very important for you because you actually arranged this entire scientific programme. First of all, can you tell me what was in your mind in planning the profile, the overall content of this meeting, as compared with, for instance, meetings in your own country, the USA?

Well we have 3,000 clinicians participating in this meeting from all different parts of the world and of course the interests and the needs of clinicians in various parts of the world might be quite different than they are in the United States, for example. So we wanted to make sure that we covered the depth and breadth of the specialty with a particular focus on what some of the needs would be for emerging economies and third world countries as well.

So what were those?

For example, in the United States cervical cancer is on the decrease. Women in Western civilisations have access to screening, much wider access to screening; there is access to vaccines that are now available to try to prevent infection with human papilloma virus, which is the causative agent in the majority of cervical cancers, whereas other less developed countries don’t have access to screening and cervical cancer is a huge problem. So in setting up the meeting we thought it would be a good idea to present a lot of the current on-going and completed studies that have been performed with cervical cancer vaccines.

So give me the story on some of these.

Some of these vaccines, there are several companies that have vaccines in trials: Merck Sharp and Dohme, Glaxo Smith Kline. These vaccines have been shown, as has presented at this meeting, to be effective in preventing infection with human papilloma virus and these are currently what’s called the quadrivalent vaccine, there are many different types of human papilloma virus, what these vaccines do is they’ve been developed to really target the four most common subtypes that are associated with cervical cancer. The vaccines are important because if you don’t have access to screening, don’t have access to getting a Pap smear on a regular basis, like women in Western societies might do, this is perhaps an effective strategy to prevent cervical cancer – just vaccinate the population. We’re talking about young women between the ages of 11 and 21.

Even if you do have access to screening though, it’s presumably a good idea to protect yourself against this disease. Is it just young women and young men and what do you think should be a rational policy of vaccination?

Certainly before somebody becomes sexually active, screening might detect a lesion at an earlier stage but the vaccine will prevent infection and that’s the whole purpose of this.

So would you recommend all schoolgirls and perhaps schoolboys as well?

It’s a controversial area; I certainly have my biases, I think it’s a good idea. I think that we know that this is a preventable disease, one of the most common causes of cancer deaths in the world in women is with cervical cancer. I think if you can prevent cervical cancer by vaccinating young women, I think it’s an excellent idea so I’m a proponent of it. I don’t think there have been any studies showing that there are major side effects or disadvantages of vaccination. I certainly had my own daughter vaccinated.

And ovarian cancer is a big issue here in Prague, what have you got for us here?

Ovarian cancer, there are many exciting developments in the treatment of ovarian cancer. Classically it’s a disease that is detected at a later stage because we don’t have any effective screening for ovarian cancer. So the majority of women that present with the disease will come in with advanced stage disease where it has spread to the upper abdomen and the primary treatment is surgery, which is what we call debulking, an effort to remove as much of the gross tumour as possible. There is some evidence now that perhaps we can equally treat these women by giving chemotherapy first and then doing these ultra-radical operations. There is morbidity associated, there are side effects with doing these big operations, and a large European study recently showed that eventual outcome was equivalent if you gave patients chemotherapy and then performed a less radical operation versus performing a radical operation up-front. In fact, this afternoon we have a debate by international experts on this topic and I don’t know if there is a consensus; there are certainly many biases as to what’s the best way to do it and I think the answer is somewhere in the middle. I think you have to select the right patients to operate on and you have to select the right patients for neoadjuvant chemotherapy.

So the whole issue of surgery in ovarian cancer is undergoing an evolution; in terms of treatment, many exciting new drugs. The median survival for ovarian cancer used to be about a year and now patients who have what we call an optimal debulking, which ideally is where you remove all of the disease or at least leave nothing more than 1cm in diameter, those patients have an average survival in the order of five years. So we’ve definitely made major improvements in the outcome of women with ovarian cancer. The big news, of course, which is being presented today at the meeting is a European study confirming the results of the United States study looking at bevacizumab, the antiangiogenic agent, the agent that blocks blood vessels in combination with classic chemotherapy for ovarian cancer. It looks like that agent might increase what we call progression free survival, the time which it takes the disease to progress or recur, but the jury is out on whether or not it improves ultimate survival.

So, in a nutshell, you’ve got an extension of survival in optimally debulked patients, possibly with neoadjuvant therapy instead of that and you’ve made big improvements on taxol platinum therapy. There’s a possibility that you might improve with molecular therapies, how big would you make that possibility?

This is the way that cancer chemotherapy is going. We have these toxic agents, which is what chemotherapy is, which have many side effects. But now we’re trying to target biological pathways and that’s what these antiangiogenic agents do, they block blood vessel formation, so in a sense starve the cancers as well. As I said, it looks like they increase the time before the cancer comes back but we don’t know if ultimately that translates into an improved survival. Plus bevacizumab, for example, those benefits were seen in patients who took what we call maintenance therapy where they continued the medication for a year after completion of chemotherapy in addition to taking it during chemotherapy, and there are side effects associated with bevacizumab.

Apart from bevacizumab, are there other targeted therapies that are beginning to look promising in ovarian cancer or indeed other gynaecologic cancers?

All gynaecologic cancers are being looked at, looking at various inhibitors of various pathways. In endometrial cancer what we call mTOR inhibitors are being looked at; ovarian cancer, there is a group of patients that have hereditary ovarian cancer which is associated with mutations in certain genes, the BRCA1 and BRCA2 genes which are associated with hereditary breast and ovarian cancer syndrome. Those patients appear to have a better prognosis and respond better to chemotherapy, in a sense because the BRCA gene is involved in repair of DNA damage. So when the cancer cells are damaged by chemotherapy because the BRCA protein, the gene that produces the protein, it can’t repair the damage from chemotherapy as well, the cells are more responsive to chemotherapy. Eventually, however, they are able to overcome that and then they start to grow and become resistant. The biological agent that is used to counteract that is what we call the PARP inhibitors and that may be of particular benefit in patients who have ovarian cancer that is associated with a BRCA mutation.

Uterine cancer is also featured in your programme, isn’t it?

Yes, we have a lot of talks on uterine cancer, very, very big time of change in the surgical management of uterine cancer. Two large trials from Europe both questioned the benefit of routinely removing lymph nodes in women with uterine cancer who undergo a hysterectomy. Removal of the lymph nodes, what’s called a lymphadenectomy, is associated with morbidity. It can cause permanent morbidity, which is lymphedema, swelling of the lower extremities which can be very disfiguring and cause major problems in terms of quality of life. Two large studies from Europe showed no benefit to doing a lymphadenectomy in randomised trials of removing lymph nodes versus not removing lymph nodes. I would say the majority of clinicians in the United States are strongly in favour of comprehensively staging patients and removing lymph nodes. So we’re at this crossroads where we’re trying to decide should we remove lymph nodes in everyone, should we remove it in only patients deemed to be at high risk for spread to lymph nodes? One of the exciting things that is being highlighted at the meeting this year was a symposium on sentinel lymph node mapping which is done in breast cancer where you inject a dye, in this case in the uterus, and try to map out the sentinel nodes which are the first nodes in the chain, try to find out the status of those nodes and if they’re negative, you don’t have to worry about the rest of the nodes because they are, in a sense, the gatekeepers. So we’ve had an exciting symposium on the development that’s occurring in sentinel node mapping, in uterine cancer and other gynaecological cancers, and we have a very big debate this afternoon by the two lead authorities in the European studies taking the anti lymph node removal position against the two experts from the United States who are very pro removing lymph nodes. I think that’s going to be a very interesting debate.

Of course, evidence base is king - how much new evidence is emerging, really solid, randomised study evidence data?

There’s quite a good amount of solid randomised data and that’s the problem. We have randomised data performed in one country showing that there’s a benefit to doing things and then in Europe you have randomised trials telling you that you don’t need to do it. So therein lies the problem – we have to try to figure out exactly what’s best for our patients. In the United States, the trial of neoadjuvant chemotherapy that was conducted in Europe showing that there was equivalent outcomes whether you operated on ovarian cancer first or gave chemotherapy first, that trial is going to be conducted in the United States. I think clinicians in the United States were a little bit concerned about the type of surgery that was conducted in the European trial and the feeling was that it wasn’t to the degree of aggressiveness that perhaps some clinicians in the United States might do.

So if you were to boil down a few clinical messages that the doctor who is daily faced with decisions to make, coming out of this meeting here in Prague, what would your brief message be?

My brief message is stay tuned, a lot of things haven’t been solved yet. There are no exact answers, I don’t think. Short of the cervical vaccines, I don’t think there’s any clear pattern emerging in terms of whether or not to remove lymph nodes for uterine cancer, I think it’s an evolution. I think we have to be a lot smarter about who we stage. I think the message for ovarian cancer will be that you have to select which patients you think you can remove all of the disease and those patients will benefit from surgery but perhaps a more elderly patient with other comorbid conditions and other features on their exam or their imaging studies would show that you can’t remove their disease, those patients probably should get treated with neoadjuvant chemotherapy. But the bright message for cervical cancer prevention is that these vaccines do appear to work. I personally think it’s an excellent idea for young women to be vaccinated and evidence now for young men as well, obviously, but especially in under-served areas, in a sense third world countries where there is really a lack of access to screening, deaths from cervical cancer is huge. So if we can prevent cervical cancer by getting these women vaccinated, in a sense we might overcome the problem of lack of access to screening. I think that’s probably one of the more hopeful messages that will emerge from this meeting.

Richard, thank you for joining us here on ecancer.tv and I hope to hear lots more from you in the future.

Thank you.