Personal Medicine for Lung Cancer
Cancer Newsline Audio Podcast Series
Date: June 01, 2009
Duration: 0 / 16:39
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Doctor Ed Kim:
to Cancer Newsline, a weekly podcast
series from the
Doctor Roy Herpst:
Ah thanks! It's a pleasure to be here.
There were several important lung cancer studies that were presented at this years meeting. Can you give us some context of where we are currently with the state of cancer treatment today, and how we're moving in a direction for our patients with the greatest needs?
It's quite important to note that the therapy for lung cancer really has been improving. In the last several years we have noticed this. Now at the last 3 or 4 ASCO's that now we have specific targeted agents that have shown a survival benefit in this disease, and the two agents, of course, that are FDA approved would be Bevacisumab, which is an antibody that, that targets blood vessels, which are critical for the growth of tumors. Which, when used with chemotherapy, improve survival in the upfront therapy of lung cancer, and then the drug Erlotinib, which is an oral agent, which is used as a single agent to a failed chemotherapy, and includes survival there as well. And both these agents came to the clinic after years of study, many of which were done at M.D. Anderson. So it's very satisfying for us to see those agents now in common use.
Now Doctor Roy Herpst, what pathways do these drugs target and, and why are they relevant in cancer?
Well we've learned, you know, a great deal in the last few years about how cancer cells grow, what are the critical pathways, what are the critical issues that, that allow them to, to divide and to grow, and to cause patients harm. One is a pathway known as the epidermal growth factor receptor pathway. That's what this drug Erlotinib targets and that's a pathway, which is up regulated and, and quite active in most patients with lung cancer. If you block that the cancer cells won't grow as well, they won't spread as well, they won't be as metastatic, and hopefully you can control the disease. The other pathway that I mentioned was angiogenesis. The idea that if you have a tumor, for a tumor to grow in its primary location, and also for it have the ability to pass through the bloodstream, spread and take up roots someplace else, it needs to form and induce new blood vessels, process of angiogenesis. And the drug Bevacisumab works to target that pathway as well. So with these two agents we, we certainly have improvements in the, in the daily care of patients with lung cancer. Though we don't want to stop there, the, the idea now is how can we do better? There are two ways to do that. One would be to develop better agents. Perhaps an agent that targets multiple pathways at the same time, just as if you were fighting a war you might want to attack in two directions at the same time, and there, thereby have a better affect against the enemy. The other, of course, would be to select your patients more carefully, to understand who is going to benefit most from any of these therapies, that would be the development of predictive factors that could tell us which drugs to use in which patients. I think both approaches are important, and perhaps we can discuss them both today.
Now you have quite a bit of experience in, in this type of co-targeting. Last year you reported some data from a study that you can share with us that showed some promise of integrating both targeting the epidermal growth factor receptor and the vascular endothelial growth factor.
Right! Over the last five years now we have looked at combinations of targets and it makes sense, because if we know that these tumors are dependant on their vascular supply, and they're also dependant on the epidermal growth factor receptor, why not target both at the same time? And we've actually gone from phase one all the way through to a phase three study that have shown some affect of, of giving both the drug Bevacisumab, it's IV, it's an antibody, and the drug Erlotinib, it's the pill, together. Those are, are data we've presented at ASCO in the past. But this year we actually have a different agent, known as Vandetanib. The thing that's nice is that's everything in one pill. So it's completely oral. In that pill we have activity against the epidermal growth factor receptor and against the blood vessels. And here we have a study where we actually used the drug with Docetaxel. With, with a common chemotherapy that's used in patients who have failed at least one chemotherapy for lung cancer.
So this was the study that was presented at the ASCO press program, clearly a very large study that builds on the experience and correct me if I'm wrong, but that early combination therapy of Erlotinib and Bevacisumab was something born out of here at M.D. Anderson through your guidance. And now if you could talk about the trial you're presenting this year with the combination of the pills and detanib with Docetaxel, and how a, it's importance and now relates to other lung cancer findings.
the idea of co-targeting the two pathways is a, is one that came out of work in
the laboratory here at M.D. Anderson. It then went to early phase trials. The
agent we're taking about today, Vandetanib, the early
phase studies were done by ourselves at M.D. Anderson. Actually Dana Farber and
other sites, actually the principle investigators there, Bruce Johnson and John
Haymac, close colleagues on several of our grant
funded programs, and we're very involved in those early studies. In fact Doctor
Haymac since has come to M.D. Anderson where he's now
a member of our group. And the idea is that this drug Vandetanib,
in a pilot study when it was used with Docetaxel, it
appeared in that small study with only 120 patients, that there was a benefit.
Meaning when you gave the drug Vandetanib, the dual
inhibitor, with the Docetaxel, it appeared that there
was an increased time to progression. Meaning it took longer for the tumor to
grow when you gave it two drugs versus the one drug, Docetaxel,
to standard therapy alone, and that was a manuscript published last year by
Doctor Haymac as the first author and several of us
in the group, of course, we're involved as well, including myself. So then we
launched, and actually we launched this several years ago, because we knew the
results, as is often the case, the results are known before they're actually in
final form and published. Two or three years ago, we organized a large
multi-national trial, almost 1,400 patients worldwide; this included the
So clearly this is a study that could change the way we practice in second line lung cancer in the future.
Um, one would think so. Let me tell you the results and, and you can judge for yourself. So basically in this study the first important point is that it was safe. You could give this drug Vandetanib with the Docetaxel therapy. While there was some increased rash and some increased diarrhea, some loose stools, which are often seen with these small molecule type agents, there really was very little else that, that strikes the eye that, that made that combination therapy worse. One thing we were very concerned about was pulmonary bleeding. Because this is something you see often see with agents that target angiogenesis, that target blood vessels and we did not see this in the trial, in 1,400 patients or so around the world. Now we did see that the therapy appeared to be better. We met our primary endpoint. We were looking to see if we can improve the progression free survival, and in fact we did that in a significant way. Patients had close to a month improvement in the time it took for their tumors to get worse. We usually portray that with a term known as the hazard ratio, and that hazard ratio was 0.79, which in my opinion is a reasonable benefit for this combination therapy, especially in light of the symptom benefits that were seen as well. One of the slides that I'll show at my presentation actually looks at patients and asks them through the questions to see how they are feeling and to see what their symptoms are from their lung cancer. And we actually were able to show that not only did the patients tumor progress more slowly, but their symptoms progressed more slowly as well. Now the ultimate endpoint for any trial in lung cancer is overall survival. Unfortunately this trial did not show a survival benefit within statistical significance. There was, in fact a nice trend. But that doesn't completely surprise me, because now a days, as we talked about earlier, with many of the advances that we've seen in lung cancer, we now have other therapies patients can get once they're off of the trial. So it's quite likely that what's happened is many of these patients after they completed therapy, either with the treatment arm or the placebo arm, went on to get other therapies, which would confound the ultimate results. But nonetheless we have what I believe is the first trial of an oral agent targeting either epidermal growth factor or vascular endothelial growth factor, and that's the thing, we don't know which activity if, or perhaps both, are important for this affect, that was, was safe and affective in this disease. So we're quite excited to be bringing these data to the community now for their peer review, and for, for their input. And whether or not this becomes a standard of care will, there, there are many steps before that can happen. But the first is here at this ASCO meeting where investigators from a large multi-national team led by ourselves at M.D. Anderson are, are presenting these data for review.
Now you mentioned the biomarkers and other aspects, and really personalizing therapy is becoming the forefront. What are we gonna see at ASCO? Or what have we moved in that direction?
know it is funny Ed, you know, the theme of ASCO is personalized therapy for
cancer, and that's been our theme in our lung program now for more than five
years, and of course, you know as well as I, as we are very closely involved in
the development of our
as you mentioned, you know I am presenting
So I think you really emphasized that, that it really does truly take a team approach. I think at M.D. Anderson here we have this, sort of multidisciplinary approach. Thanks so much for having this discussion with me today. I think we've really found some significant findings that our listeners will be interested in. If you have any questions about anything you've heard today on Cancer New Line, contact Ask M.D. Anderson at 1-877-MDA-6789 or online at www.mdanderson.org/ask. Thank you for listening to this episode of Cancer Newsline. Tune in next week for the next podcast in our series.
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