2015 ASCO Annual Meeting Research Round Up – Sarcoma, with Robert G. Maki, MD, PhD, FACP

July 28, 2015
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In this podcast, Dr. Robert Maki discusses some of the research on sarcoma presented at ASCO’s 2015 Annual Meeting. 

Transcript: 

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ASCO: You are listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO; the world's leading professional organization for doctors that care for people with cancer.

In today's podcast, we'll discuss some of the research on sarcoma presented at ASCO's 2015 Annual Meeting. This podcast will be led by Dr. Robert Maki, who is professor of medicine, pediatrics and orthopedics, and the Steven Ravitch Chair in Pediatric Hematology-Oncology at Mount Sinai School of Medicine. Dr. Maki is also an Associate Editor for Cancer.Net.

The ASCO Annual Meeting is the premier educational and scientific event where physicians, researchers, and other healthcare professionals gather to discuss the latest in cancer care and treatment. The cancer.net podcast helps put new research findings into context, and explains what they mean for patients. ASCO would like to thank Dr. Maki for summarizing this research.

Dr. Maki: Hi this is Bob Maki. I'm a medical oncologist who studies sarcomas. And today I would like to discuss some research on sarcomas that was presented at the ASCO 2015 Annual Meeting. I would also like to point out that the number of presentations on the ASCO University website that go into much more detail regarding the adjuvant therapy and the treatment of metastatic disease for people with sarcomas that are very nice presented by a number of experts in the field, and are worth your review as well. That said, I'm going to focus on some presentations from the oral session at the 2015 meeting. Most of these will focus on metastatic sarcomas, in other words, sarcomas that have come back. Although I will mention one adjuvant study, an update of study of, on GIST gastrointestinal stromal tumor that gave us some more information on the overall survival of people who received iMet and had been in the adjuvant setting.

But first, I'd like to focus on the studies involving metastatic sarcoma, and the first of these is the GeDDiS study or the G.E.D.D.I.S study. This was presented by Beatrice Seddon and her colleagues and was performed in the United Kingdom. This is a study that enrolled about 250 people and looked at one of two standard treatments. The first was Doxorubicin, a drug that's been used for many years as standard treatment for metastatic sarcomas. The other combination is Gemcitabine and Docetaxel. And this is the combination that we use frequently but it's not clear which treatment is better. And our colleagues in the United Kingdom put together a study of 250 people to try answer the question. What they found was the treatments really were pretty similar in terms of their outcomes, at least up to about half a year or so. After about half a year, it seems, there may have been a slight benefit towards giving the Doxorubicin therapy as opposed to the slightly new accommodation of Gemcitabine and Docetaxel.

Now, there are about 50 different types of sarcoma and this data were not broken out by specific sarcoma subtypes. And so for example, for a common subtype such as undifferentiated pleomorphic sarcoma, I still think that the Gemcitabine and Docetaxel combination may be superior, but not that many people with that diagnosis will put on this study. And at least at a first pass, it's pretty clear that Gemcitabine and Docetaxel is not vastly superior to Doxorubicin. And so the simpler, single drug Doxorubicin remains a very good standard of care for people who need treatments in first-line once their sarcoma has come back.

There are a couple of randomized studies that also may change the standard of care for people who have recurrent sarcomas that have failed first-line therapy as well, and two of these presentations give some guidance in that direction. The first of these was a study presented by Patrick Schoffski and colleagues, and looked at the drug eribulin and compared that drug to dacarbazine, another drug we've had around for a very long time for treatment of sarcomas. Eribulin's already available and approved in many countries for treatment of breast cancer, and Dr. Schoffski and colleagues compared one treatment to the other. And what they found was a statistically significant improvement in terms of survival, overall survival, in people who received eribulin versus dacarbazine. Now, people stayed on treatment for about the same period of time, but overall survival was better with eribulin. That's one of the strongest endpoints that we have in clinical trials, and it may end up allowing for approval on a standard basis of eribulin in the United States and elsewhere. However, these sorts of data will have to be analyzed and looked at very carefully by the regulatory authorities, and they are the ultimate arbiters of whether these data are strong enough to allow for eribulin to approved for use in metastatic sarcomas.

In a second study, another drug that we know is useful in sarcomas called trabectedin was compared to dacarbazine. Trabectedin is already approved in Europe by virtue of a prior randomized study, but it was not approved by the FDA and so that is part of the reason this particular study was conducted. Again, people with liposarcoma or leiomyosarcoma were examined in this particular trial comparing trabectedin or dacarbazine, and the results were, again, fairly solid. People stayed on trabectedin for a longer period of time than people stayed on dacarbazine. Although there was no difference in the ultimate overall survival of people who received one treatment for the other, and there are a number of reasons for that that I won't go into just now. That said, since people stayed on trabectedin for longer, they had longer progression-free survival, as it's called. These data may be strong enough to allow for the drug to be approved, especially in the setting of there being another randomized study showing that trabectedin was useful as well. Nonetheless, these data will have to be reviewed by the regulatory authorities, and the authorities will let us know whether this drug will be acceptable or not as a novel therapeutic for people in general, for people with sarcomas.

Some of the most exciting data from the meeting were presented by William Tapp and colleagues.  This involved again the standard drug doxorubicin plus or minus a new compound and this is a monoclonal antibody. A drug called olaratumab, or 3G3, and this is an antibody that blocks a special signal which is sent to tumor cells and surrounding cells by the molecules called PBGF receptor alpha. This drug was studied for the first time in the randomized fashion in this particular study and was a roughly smaller study, in which people received either the doxorubicin alone or the doxorubicin along with olaratumab.  And of the 133 people who were treated, it was clear that people stayed on the two drug treatment longer than they stayed on the one drug treatment and, in fact, people who received the two drugs together lived longer as well, as the people compared with the people who received doxorubicin alone. The overall survival analysis now showed that the survival was about 25 months for people who received two drugs against about 15 months if you received doxorubicin alone. So these are promising data, but we also know that there have been similar promising studies that are small studies like this that did not turn out to be so positive once phase III or larger clinical trials were done. So unfortunately, these data will most likely have to be replicated in the larger fashion to either confirm or refute the usefulness of the two drugs versus the one drug. None the less, these are exciting data of a new class of compounds that we didn't really have access to previously.

Well, that does it for discussion of the treatment of metastatic sarcoma. I'd like to focus, finally, on one of the more common types of sarcoma, GIST gastrointestinal stromal tumor. As there was a nice update on a well-recognized clinical trial from Hsueh Yuan-Shuo and colleagues, and this is the study that looked at three years of imatinib, a drug called Gleevec as well, compared to just one year of imatinib. And the previous presentation from Dr. Yuan-Shuo, we learned that survival was better if he received three years of imatinib instead of just one year of imatinib. And this has become a standard of care for people who have primary, just in other words, just that it's just been cut out for the first time. Dr. Yuan-Shuo kindly updated us now that there are five to ten years of follow-up of people on the study and we learned that the overall survival for people who received five years of therapy was about 93%. And the survival of people who received just one year of imatinib was 87%. And these data confirm the idea that a longer exposure to imatinib helps improve the cure rate. Now, this data will be followed up with a future study, and Dr. Yuan-Shou is now going to lead a trial of five years of imatinib versus three years of imatinib. Now, we know already that in a metastatic setting, three drugs are approved in many countries, namely imatinib in first-line metastatic disease followed by sunitinib and most recently, regorafenib are all approved from metastatic disease. But it's pretty clear that even though there's very good survival of most people who received three years of imatinib that we still have work to do, and certainly people who have metastatic GIST also need some new options. We hopefully will see some new combinations of drugs moving forward and also in the near future.

Also, we have not seen much data on immunotherapy in sarcoma as you've probably seen in ASCO in the late press, a number of presentations, and data, that new checkpoint inhibitors, as they're called, can be useful in a number of cancers such as lung cancer and bladder cancer, as well as melanoma and kidney cancer. We don't have those sorts of data for sarcoma yet because unfortunately it's been difficult to get access to these compounds for study in sarcoma. But, the good news is these studies are finally underway and we'll hopefully have some initial data on these novel therapeutics for the 2016 ASCO meeting, as well as an analysis of other novel compounds. I hope this has been a useful discussion for you and again please tune in to the ASCO University website if you'd like some more details on management of sarcoma. Thank you very much for your time and listening to this presentation.

ASCO: Thank you Dr. Maki. To find all of the science presented at ASCO's 2015 Annual Meeting, visit www.cancer.net. If you have questions about whether new research may affect your care, be sure to talk with your doctor.

Cancer.Net is supported by the Conquer Cancer Foundation, which is working to create a world free from the fear of cancer by funding breakthrough research, sharing knowledge with physicians and patients worldwide, and supporting initiatives to ensure that all people have access to high quality cancer care. Thank you for listening to this Cancer.Net podcast.

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