Professor Christopher Twelves, MD: Advancements in Metastatic Breast Cancer from ASCO 2011
Professor Christopher Twelves, MD is Clinical Director and Professor of Clinical Cancer Pharmacology and Oncology, & Head, Clinical Cancer Research Groups, Leeds Institute of Molecular Medicine and St James’s Institute of Oncology. Professor Twelves gives an overview of the exciting advances in metastatic breast cancer surrounding the new treatment, Halaven (eribulin mesylate) at ASCO 2011.
The Group Room at the 2011 American Association For Cancer Research Annual Meeting was made possible, in part, by:
VIDEO TRANSCRIPT
Selma R. Schimmel, Founder & CEO, Vital Options International
This is Selma Schimmel at the 2011annual ASCO meeting in Chicago, and we are beginning our interviews with many of the most prominent key opinion leaders so we can bring you firsthand information directly from the source. I am so happy to be able to welcome you now, Professor and Honorary Consultant in Medical Oncology, Dr. Christopher Twelves. Hello, Dr. Twelves.
Professor Christopher Twelves, MD, Deputy Dir. of Cancer Research, St. James’s Hospital, Leeds, UK
Hello, nice to meet you.
Selma R. Schimmel:
You are also the Head of Experimental Cancer Medicine at the St. James’s Institute of Oncology in Leeds, which is the United Kingdom.
Professor Christopher Twelves:
That’s right, that’s right.
Selma R. Schimmel:
And you’re a very important guy because you have been the principle investigator of a study that really is changing the face of breast cancer for women that are living with metastatic disease, and I say living with because I think that’s such an important distinction.
Professor Christopher Twelves:
I think one of the important things that I’ve been very focused on over the many years I’ve been treating women with breast cancer is just like the women you described, the women whose cancer has relapsed but we want to help live forth as long as we possibly can and to maintain their lifestyle. And we see, quite understandably, so much focus on adjuvant therapy because of the potential to cure the disease, and that’s quite right and appropriate, but there are many women, unfortunately, for whom the cancer does come back and I think it’s important we don’t lose sight of those women and how we can help them.
Selma R. Schimmel:
So, let’s talk a bit about your research and what is so distinguishing about it as compared to some of the other therapies; and again, we’re talking about women with metastatic breast cancer.
Professor Christopher Twelves:
Well, the study that you’re talking about and that I presented at last year’s ASCO is with a new drug called eribulin or halaven, as it’ll be known. This is a new type of chemotherapy drug and it’s one that originates, rather interestingly, from a marine organism, from a sea sponge. And this was discovered, literally, decades ago from a sea sponge that was found on a sea bed near Tokyo and the scientists that took extracts from this sea sponge and discovered that one of them was quite toxic or very toxic to cancer cells.
Selma R. Schimmel:
How does a scientist… you find a sea sponge, but how does a scientist begin to put the pieces together and realize that the toxic nature of it can fight cancer?
Professor Christopher Twelves:
Well, interestingly, quite a few of the chemotherapy drugs that we use already, drugs such as patataxil, the vinca alkaloids, also originated form organisms that are natural extracts. This is something that we sometimes forget, that many of the drugs that we use originate from mainly land-based organisms. And about 15-years, 20-years ago, people started to think that the majority of the earth’s surface is water and therefore this was a potential source of other chemicals that may be used to treat cancer. And also, starting to think that the marine environment, in many ways, is a very hostile environment and that potentially, the organisms that lived under the sea, for them to be able to survive, things like sea sponges, that they would need really quite complex defense mechanisms and therefore, that they may harbor potential poisons that we may be able to extract from these organisms and then use it in a constructive way.
Selma R. Schimmel:
Where is the research now? At the time it was a phase 3 trial, where is it today?
Professor Christopher Twelves:
Well, we had a very exciting year in that it was only just over a year ago that we got the results of the phase 3 trial – and the trial had the name Embrace – and we presented those results at ASCO last year showing that eribulin was able to prolong survival for these women living with metastatic breast cancer and that was followed by a publication in The Lancet public medical journal just a couple of months ago. And in the meantime, we’ve had the drug approved by the regulatory authorities in the US, in Europe and also in other countries, I think, including Singapore and Switzerland. So really, over the last 12-months things have moved on really at a pace.
Selma R. Schimmel:
Last year the president of ASCO said that this is potentially a practice changing drug, explain that.
Professor Christopher Twelves:
Well, I think that is right and maybe the way that I can explain it is to put halaven in the context of where I see it being used. Because these days we have a diminishing proportion, but still, we have women whose breast cancer comes back where we need to control their disease for as long as possible. For many of these women, they don’t have disease which is sensitive to hormonal therapy so we are reliant on chemotherapy. And we have a number of drugs that have got a proven track record; drugs such as the anthracyclines, the taxanes, capecitabines or xeloda, which we know are active in this setting. But for many women, they can respond to these treatments for a while but then their cancer becomes active again. And when we’ve exhausted those tried and tested drugs we haven’t, up until now, had a chemotherapy or other treatment that was a proven benefits. We had a range of drugs which we knew could work in earlier stages of breast cancer, though we would often try and hope that they would do some good for these women who were more heavily pre-treated but we didn’t actually have proof that these drugs were able to prolong survival; and that’s where halaven has changed the environment and, I think, become a new standard of care.
Selma R. Schimmel:
And this is a chemotherapy agent that is used in combination with a targeted therapy in appropriate cases?
Professor Christopher Twelves:
At the moment, it’s used on its own. Now it’s interesting that you raise the concept of the targeted therapies because eribulin is a chemotherapy drug – and I apologize for moving between eribulin and halaven, I know it by both names – so this is a chemotherapy drug and it works in an interesting way that is the same but different to other chemotherapy drugs. So what it targets are what we call the microtubules within the cell – and that’s, if you like, the scaffold that helps the cell divide, it pulls the chromosomes apart – and that’s the same target that other drugs such as paclitaxel, docetaxel, the vinca alkaloids target. So we know that attacking the microtubules is a good way of treating women with breast cancer. Where eribulin is different is that it targets this molecule, this structure, the microtubule in a different, much more specific way. And it appears that targeting the microtubule in this subtly different way means that it has a different pattern of activity in the laboratory and may be able to work in situations where the drugs that we previously have have not been able to work.
Selma R. Schimmel:
What kinds of side effects are associated with the compound?
Professor Christopher Twelves:
Well, as with any, I was going to say chemotherapy, but really any treatment of breast cancer there are some side effects but these are relatively modest. As clinicians, we often use the term manageable or acceptable, which is a bit of an impertinence since it is our patients who should decide how acceptable the side effects are. But, having said that, in the context of the side effects that we see our patients experience with other chemotherapy drugs, these side effects are really quite modest. Eribulin, halaven can affect their blood count so we do have to warn patients that they may develop infections but some other side effects that we thought might be a problem, such as neuropathy, which is tingling in the fingers and toes and sometimes even weakness of the hands or feet. This isn’t something that we see with any great frequency. We do see it in a minority of patients, less than 10% of patients but by reducing the dose of the drug or delaying the treatments, we can allow that to settle down and continue the therapy.
Selma R. Schimmel:
So, unlike some of the taxanes, like where you would experience that?
Professor Christopher Twelves, MD, Deputy Dir. of Cancer Research, St. James ’s Hospital, Leeds, UK
Yes, some of the taxanes and some other drugs which also target the microtubules, we’ve seen that really a substantial proportion of patients get nerve damage that can be really quite troublesome. For eribulin, it’s very much a small minority of patients who are affected.
Selma R. Schimmel:
What about hair loss?
Professor Christopher Twelves:
Hair loss is tricky to know and you may think that’s a strange thing to say, but most of the experience we have with halaven is in treating women who have received many lines of prior chemotherapy. So, most of the women who have been treated with halaven have already got hair loss to a greater or lesser extent from their earlier treatment. So we really won’t know until we start treating women who have not received previous chemotherapy, who start with a full head of hair, we won’t really know until then. Our sense is it can cause some hair loss but certainly nothing like as much as many other drugs and that quite often women can get some regrowth of their hair once they’re on halaven.
Selma R. Schimmel:
And you may get that answer soon because the goal is to see how effective the drug can now be for an earlier stage of breast cancer?
Professor Christopher Twelves:
That’s right. We already have completed accrual to a trial so that another trial in which women who were slightly less heavily pre-treated than in the trial that we presented last year; we’ve already completed that trial and are awaiting the results and the analysis. And, but having seen the really very encouraging results from last year’s study, a new generation of trials is now being planned and some of those will certainly look at halaven in women with much earlier stages of the disease.
Selma R. Schimmel:
And, Professor Twelves, the criteria for a woman getting the drug at an earlier stage, granted it is a research study, but what was or would be the criteria for that sort of early stage breast cancer patient? In other words, would she have to present a certain way clinically in order to benefit from the drug?
Professor Christopher Twelves:
Well, in the coming months and years there will be a program of clinical trials for women who have less heavily pre-treated disease and there will be information on the internet about which centers are running those. For women who are receiving halaven or are interested about halaven in the standard setting, the situation in which it has been approved is in women who have received previously treatment with anthracyclines, taxanes, and were in the situation where there are really often few, if any other options with a proven benefit.
Selma R. Schimmel:
And in a metastatic setting, the early research increased survival was, I think, 2.5-months, but since then you have a bit more research. How is it looking for the landscape for overall survival?
Professor Christopher Twelves:
Well, what’s most encouraging is that we are seeing this benefiting survival. When I was training in breast cancer, some 15-20 years, I should say 20-25 years ago I’m afraid, it wasn’t at all clear what impact chemotherapy had for prolonging survival. We were taught that the main aim of chemotherapy was to reduce or prevent symptoms developing and that was helpful for women but it really wasn’t clear what the impact on survival was. What we’ve seen over the last 10 years, in a limited number of trials is that we clearly can prolong survival for women with metastatic breast cancer. And this group of women who’d exhausted the tried and tested therapies, as you say, survival was increased from about 10.5-months to just over 13-months when we presented the data last year. Since then we’ve done some further analysis that the regulatory authorities asked for and that shows that as the data mature that the benefits are becoming more apparent, the increase in survival is a little bit more than that, about 2.7-months, but I think what’s encouraging is that as the data get more mature the results get more encouraging. What we sometimes have seen in the past is promising early results wither away as the data mature, when we look to be seeing quite the opposite. The other analysis that we’ve done, which I think is relevant to many of my patients and to many people who will be looking at this, is that when we looked at the patients who were treated from North America, from Europe and from Austral-Asia, the benefits from eribulin appear to be particularly marked in that group of women where the prolongation of survival was over 3-months.
Selma R. Schimmel:
One of the noted breast physicians said that he feels that this could be the last chemotherapeutic agent being developed for the treatment of breast cancer. What do you say about that?
Professor Christopher Twelves:
I think it’s an interesting comment. Certainly there are relatively few chemotherapy drugs being developed that have reached the stage of these large phase-3 trials and where it will be the last I rather doubt that. Chemotherapy is still the core; it’s still the foundation of our treatments for metastatic breast cancer. Most patients who receive herceptin, for example, will also be receiving chemotherapy.
Selma R. Schimmel:
It’s combination therapy.
Professor Christopher Twelves:
It’s combinations; so I think we’ll continue to see more chemotherapy. I think what we may see emerge over the coming years is a breaking down of this distinction between chemotherapy drugs on the one hand and targeted therapies on the other hand. If we use halaven as an example, we understand very clearly how it works; it targets the microtubule in a very precise way. So I think this middle ground where we’re developing new chemotherapy drugs, but ones that are targeted in a sense that we’re developing them on a basis of how we understand what makes the cancer cell tick means that there may be a new generation of drugs that are, if you like, smart chemotherapy rather than the less smart drugs that we’ve had in the past.
Selma R. Schimmel:
Thank you.
Professor Christopher Twelves:
Thank you very much.
Selma R. Schimmel:
Professor, Dr. Christopher Twelves; Head of Experimental Cancer Medicine, The Center at St. James’s Institute of Oncology, Leeds, United Kingdom.
Professor Christopher Twelves:
Thank you very much.
END OF VIDEO