Highlights from the 2014 Gastrointestinal Cancer Symposium, with Smitha Krishnamurthi, MD

January 14, 2014
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In this podcast, we’ll review some of the news announced at the 2014 Gastrointestinal Cancers Symposium, co-sponsored by ASCO.


ASCO: You're 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 review some of the news announced at the 2014 Gastrointestinal Cancer Symposium, co-sponsored by ASCO. This podcast will be led by Dr. Smitha Krishnamurthi who is an Associate Professor of Medicine at Western Reserve University School of Medicine. Dr. Krishnamurthi is also a member of ASCO's Cancer Communications Committee. The symposium, held January 16th through 18th, 2014 in San Francisco, California offers presentations on the latest multidisciplinary research for gastrointestinal cancers. Specifically, highlighted research includes news about stomach, pancreatic, and colorectal cancers as well as neuroendocrine tumors. This Cancer.Net podcast helps put new research findings into context and explains what this news means for patients. ASCO would like to thank Dr. Krishnamurthi for summarizing these findings.

Dr. Krishnamurthi: Hello. I'm Dr. Smitha Krishnamurthi. I am a medical oncologist and I specialize in patients with gastrointestinal cancer. And I work at the University Hospital Seidman Cancer Center which is part of the Case Comprehensive Cancer Center in Cleveland, Ohio. I am delighted today to discuss five of the most exciting abstracts that will be presented at the 2014 Gastrointestinal Cancer Symposium.

The first one is about treating patients who have advanced gastric cancer. This is a large randomized control trial for patients who had advanced gastric cancer and who had already received one line of chemotherapy. Patients who enrolled in the study were randomly assigned to get either the chemotherapy drug Taxol or paclitaxel with a monoclonal antibody called ramucirumab or to get the chemotherapy alone. And ramucirumab is an investigational drug, it targets the vascular endothelial growth factor receptor which is involved in tumors forming their blood supply. So inhibiting this formation of the blood supply prevents tumors from getting nutrition in and waste out. And drugs that inhibit this process are called angiogenesis inhibitors. So we already have angiogenesis inhibitors that are approved for treating lung cancer and colorectal cancer for example, but not yet for gastric cancer.

So in this study, over 600 patients were assigned to either the chemotherapy or the chemotherapy with the ramucirumab as their second line treatment. And the results revealed that patients who received that ramucirumab actually live longer. Their median survival was almost 10 months and that was compared to about seven months for patients who had the chemotherapy alone. Median means that half the patients live less and half live longer, so the median survival was improved in the patients that received the ramucirumab. Also, the patients who received the ramucirumab had a higher chance of responding to the treatment. It was 28% response rate among patients who had the chemotherapy plus ramucirumab, compared to 16% with the chemotherapy alone.

So the data were clear that the patients who received the ramucirumab had a better outcome in terms of response rate and survival. But what about at what cost? What were the side effects? So there was an increase in side effects with the ramucirumab such as more lowering of the blood cell counts. But fortunately, that did not translate into any increase in serious infections. Patients who received the ramucirumab also had some more fatigue, and abdominal pain, and weakness, but the side effects were manageable. And the preliminary data suggests that patients had better quality of life when they received the ramucirumab. So in conclusion, the study showed a two-month improvement in survival and a higher response rate for patients with advanced gastric cancer who received paclitaxel chemotherapy with ramucirumab compared to the chemotherapy alone. And these benefits came with improved quality of life.

The next study I'm going to discuss is an exciting study for patients with metastatic pancreatic cancer. This was a study that compared two different anti-cancer vaccines, the G-V-A-X or GVAX Pancreas cancer vaccine and CRS-207. GVAX is a pancreatic cancer vaccine made of pancreatic cancer cells that have been engineered to stimulate the immune system. And they're given in combination with low-dose chemotherapy called cyclophosphamide, that helps it work better. The CRS-207 is actually a weakened form of a bacteria called Listeria. And this stimulates an immune response and it's also engineered to stimulate an immune response to pancreatic cancer.

In the study, 90 patients who had advanced pancreatic cancer were randomly assigned to receive either the GVAX vaccine followed by the CRS-207 vaccine or the GVAX alone. This study showed an improvement in survival for patients who received both vaccines compared to those who received only the GVAX vaccine. The survival rate at one year was actually doubled to 24% among the patients who received both vaccines compared to 12% for those who received the GVAX alone. And when they looked at the data in terms of patients who received at least one dose of the two-vaccine combination may be at least one dose of the Listeria bacteria vaccine, they found that the survival was also doubled from approximately four and a half months to nine months.

So this was very exciting data because here we have a study in patients with metastatic pancreatic cancer who have very limited treatment options and we're actually seeing an improvement in survival with treatments that boost the immune response to pancreatic cancer. So this is the first randomized study to show an improvement survival using immunotherapy for pancreatic cancer. And so patients were able to benefit from this treatment without any of the side effects typically associated with chemotherapy. The vaccines were typically well tolerated and the side effects did not get worse with increasing number of doses. So this is very exciting and is the first of several studies that can be expected evaluating these vaccines. The researchers who conducted this study are planning to open a larger clinical trial that will be looking at the two-vaccine combination, that's the GVAX and CRS-207 versus the CRS-207 alone versus chemotherapy.

The next study I'm going to discuss evaluated a chemotherapy combination for patients with advanced neuroendocrine cancers. So neuroendocrine tumurs tend to be slow growing and traditionally are resistant to chemotherapy, particularly carcinoid tumors. Among neuroendocrine cancers, the type that responds better to chemotherapy are those that arrived from the pancreas. The study we're going to discuss now is a small study of 28 patients who had various types of metastatic or advanced neuroendocrine tumors. Some of them arose in the pancreas and others were from other parts of the intestines or from a gland in the brain called the pituitary gland. All of these patients had previously had hormone therapy with the drug octreotide. But as their cancer got worse or say were not able to tolerate it, they were then allowed to enroll in this trial.

The drugs new to this study were two chemotherapy drugs. One is capecitabine which has a brand name Xeloda and the other is temozolomide which has a brand name of Temodar. The combination was studied because researchers had found that in neuroendocrine cells in the laboratory, that this combination of chemotherapy worked well in treating neuroendocrine cancers. In this clinical trial that will be presented at the GI Cancer Symposium, the 28 patients enrolled were treated with a combination of capecitabine and temozolomide chemotherapy. And what is striking about this study and why we're discussing it even though it is a small study, is that patients responded very well to this treatment.

What's particularly notable is that the trial patients who had carcinoid tumors demonstrated benefit from this chemotherapy combination. 41% of the 12 patients with carcinoid tumors demonstrated significant tumor shrinkage. This is rather remarkable because historically, carcinoid tumors have a very low rate of tumor shrinkage in response to chemotherapy, such as 5% or less. Patients with the pancreatic neuroendocrine tumors and pituitary tumors also showed responses and the benefits appeared to be long lasting. Half of the patients who were treated did not have any growth of their disease for more than two and a half years and the chemotherapy combination was very well tolerated.

So this combination of chemotherapy appears very promising and warrants larger studies of this capecitabine and temozolomide combination. This is a small study, and so its results will need to be validated in a larger trial to definitively prove that the capecitabine and temozolomide is an active regiment for neuroendocrine cancers including carcinoid tumors. Both of these drugs however are commercially available, so patients may be able to receive this combination without being on a clinical trial. But should certainly discuss this with their doctors.

The next study I'll discuss is a large randomized clinical trial for patients with stage 2 and 3 rectal cancer. So the standard treatment for patients who are diagnosed with stage 2 and 3 rectal cancer is radiation therapy accompanied by chemotherapy to make the tumor more sensitive to the radiation. And the standard chemotherapy has been 5-fluorouracil which is also known as 5-FU. Capecitabine is a pill that in the bodies converted to 5-fluorouracil. At the time that this study was developed, there were small studies that suggested that capecitabine could be used instead of 5-FU in combination with radiation therapy. And that was of interest because when the 5-FU is given with radiation therapy, it had been found to be superior when it was administered as a continued intravenous infusion compared to getting it more intermittently. So patients received the 5-FU via a pump that connects to a central venous catheter and they receive the 5-FU over many weeks like this. So it's not a very convenient regiment and certainly would be more convenient to take capecitabine pills which are taken at home as pills twice a day.

This study was a large study which enrolled over 1,600 patients and randomly assigned them to treatment in four different groups. One group received the standard 5-FU. The other received capecitabine. Another group received 5-FU plus another chemotherapy called oxaliplatin. And the fourth group received capecitabine and oxaliplatin. So the study was really asking two questions. It was asking if 5-FU and capecitabine are equivalent, and it's also asking if there's any benefit to adding oxaliplatin to the chemotherapy and radiation. Oxaliplatin is an intravenous chemotherapy that is active in advanced colorectal cancer and it's been FDA approved since 2002. However, it was not known if it would add any benefit for patients with early stage rectal cancer.

So the results from the study showed that there really was no difference in outcome in the patients who received 5-FU or capecitabine. So because this is a large study, this provides definitive data that we can use capecitabine instead of 5-FU. So our patients have choices, and the capecitabine is more convenient and many patients would prefer it over the intravenous 5-FU. The study also importantly found that there is no benefit to adding oxaliplatin. Patients who received oxaliplatin had more side effects, but did not have any improvement in outcome. And the primary outcome of this study was local, regional recurrence. So the chance of the cancer coming back where it started. So this large study gives us definitive data that we can use capecitabine or 5-FU along with radiation for patients with stage 2 and 3 rectal cancer and that we should not administer oxaliplatin in this setting.

The final study I'll discuss, evaluated testing for mutations in the Ras family of genes. This is important because we know that about 40% of patients with metastatic colorectal cancer have mutations in the gene called KRAS, K-R-A-S, or it's called KRAS. And we know that patients who carry a mutation in the KRAS gene and their colorectal cancer will not respond to a class of drugs that inhibit the epidermal growth factor receptor. So knowing this information prevents patients from receiving a drug that would not benefit them. So it saves them from going through the side effects and the expense of a drug that won't benefit them.

In this study presented at the symposium, researchers evaluated additional testing for mutations in Ras genes. So they looked at more mutations in KRAS than we currently test for and they also looked at mutations in a related gene called NRAS or N-R-A-S. What they found is that, among patients who would be considered to have a normal KRAS gene with our currently available testing, almost 20% of them actually had a mutation elsewhere in the KRAS gene or had a mutation in the NRAS gene. And importantly, they found that patients who had these additional mutations did not have benefit from the drug panitumumab which inhibits the epidermal growth factor receptor. And also importantly is that when they looked at the patients who did not have any mutation in KRAS or NRAS based on this expanded testing, those patients actually did better with panitumumab than when it was administered to everyone based on the currently available KRAS testing.

So this study shows that as we get smarter about better identifying patients for treatment, we can spare more patients from toxicities and side effects from a drug that won't work for them. And when we do a better job at identifying patients who are more likely to benefit from panitumumab, we find that they actually do have better outcomes in terms of survival. So the data from this study - along with data from other studies that will be presented at the symposium looking at this class of drugs and expanded testing for mutations in the Ras gene family - will likely lead to a change in our current practice so that the commercially available testing for Ras gene mutations will be expanded so that oncologists can do a better job of identifying the patients who will benefit from the anti Epidermal Growth Factor Receptor therapy.

ASCO: Thank you Dr. Krishnamurthi. More news from the 2014 Gastrointestinal Cancer Symposium can be found at www.cancer.net. 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.