HonCode

Go Back   HER2 Support Group Forums > Clinical Trials
Register Gallery FAQ Members List Calendar Search Today's Posts Mark Forums Read

Reply
 
Thread Tools Display Modes
Old 05-27-2006, 08:42 PM   #1
Cathya
Senior Member
 
Cathya's Avatar
 
Join Date: Sep 2005
Location: Ontario, Canada
Posts: 752
Personalized Treatment Trial....TAILORx

Personalized Treatment Trial for Breast Cancer Launched

The Trial Assigning IndividuaLized Options for Treatment (Rx), or TAILORx, was launched today to examine whether genes that are frequently associated with risk of recurrence for women with early-stage breast cancer can be used to assign patients to the most appropriate and effective treatment. TAILORx is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), and is coordinated by the Eastern Cooperative Oncology Group (ECOG). All of the NCI-sponsored clinical trials groups* that perform breast cancer research studies have collaborated in the trial's development and are participating in this study.

"This trial is important because it is one of the first to examine a methodology for personalizing cancer treatment," said NIH Director Elias A. Zerhouni, M.D.

The majority of women with early-stage breast cancer are advised to receive chemotherapy in addition to radiation and hormonal therapy, yet research has not demonstrated that chemotherapy benefits all of them equally. TAILORx seeks to incorporate a molecular profiling test (a technique that examines many genes simultaneously) into clinical decision making, and thus spare women unnecessary treatment if chemotherapy is not likely to be of substantial benefit to them. The study will enroll over 10,000 women at 900 sites in the United States and Canada. Women recently diagnosed with estrogen receptor and/or progesterone receptor positive, Her2/neu negative breast cancer, which has not yet spread to the lymph nodes, are eligible for the study. Overexpression of the Her2/neu gene carries poorer prognosis for patients.

TAILORx will determine the most effective current approach to cancer treatment, with the fewest side effects, for women with early-stage breast cancer by using Oncotype DXTM, a validated diagnostic test developed by Genomic Health, Inc., Redwood City, Calif., in collaboration with the National Surgical Adjuvant Breast and Bowel Project (NSABP), a network of cancer research professionals. TAILORx is the first trial to be launched as part of a new NCI program, the Program for the Assessment of Clinical Cancer Tests (PACCT), which seeks to individualize cancer treatment by using, evaluating and improving the latest diagnostic tests.

Research appearing online today in the Journal of Clinical Oncology** provides strong evidence for the value of using Oncotype DXTM to help women with this form of breast cancer determine whether they will benefit by adding chemotherapy to hormonal therapy. This study, as well as several other similar studies in recent years, provided the basis for the launch of TAILORx.

Breast cancer is the most frequently diagnosed cancer in women, with an estimated 212,920 new cases of invasive breast cancer expected in the United States in 2006. Over one-half of these women will have estrogen receptor positive, lymph node negative breast cancer. For 80 percent to 85 percent of those women, the current standard treatment practice is surgical excision of the tumor, followed by radiation and hormonal therapy. Chemotherapy is also recommended for most women, but the proportion of women who actually benefit substantially from chemotherapy is fairly small.

"A large number of these women are receiving toxic chemotherapy unnecessarily, and we need a means of identifying them," said Jo Anne Zujewski, M.D., senior investigator in the Clinical Investigation Branch of NCI's Cancer Therapy Evaluation Program. "TAILORx could help change the way we treat breast cancer and improve the quality of patients' lives, helping to better identify women who are likely to benefit from chemotherapy from those who are not."

Oncotype DXTM measures the levels of expression of 21 genes (whether they are transcribed into messenger RNA) in breast tumors. This assessment can more precisely estimate a person's risk of recurrence than standard characteristics, such as tumor size and grade. Based on the Oncotype DXTM gene expression analysis, a recurrence score from 0 to 100 is generated; the higher the score, the greater a woman's chance of having a recurrence if treated with hormonal therapy alone.

Women will be studied for 10 years, with an additional follow-up of up to 20 years after initial therapies. Based on their recurrence score, women will be assigned to three different treatment groups in the TAILORx study:
  • Women with a recurrence score higher than 25 will receive chemotherapy plus hormonal therapy (the standard of care)
  • Women with a recurrence score lower than 11 will receive hormonal therapy alone
  • Women with a recurrence score of 11 to 25 will be randomly assigned to receive adjuvant hormonal therapy, with or without chemotherapy.
TAILORx is designed primarily to evaluate the effect of chemotherapy on those with a recurrence score of 11 to 25. Women in this last group will comprise 4,390 women, or about 44 percent of the study population. Because the degree of benefit of chemotherapy for women with recurrence scores between 11 and 25 is uncertain, TAILORx seeks to determine if the Oncotype DXTM test will be helpful in future treatment planning for this group.

Hormonal therapies in the trial are assigned based on menopausal status and include tamoxifen and the aromatase inhibitors anastrozole, letrozole and exemestane. Women on the chemotherapy arm of the trial will receive one of several standard combination chemotherapy regimens considered to be the best available standard care today. It will also be possible for women participating in TAILORx to participate in other NCI-sponsored clinical trials, provided the therapy prescribed in the clinical trial is consistent with their assigned therapy in TAILORx.

Additional goals of this clinical study are to create a tissue and specimen repository for patients enrolled in the trial and to collect follow-up information regarding the health status of those who participate in the study. Tissue collected in this study will be stored for use in future studies to learn more about breast cancer and to evaluate, and potentially refine, diagnostic tests for treatment decisions to an even greater degree than in TAILORx.

"With TAILORx, we are taking a big step toward personalized medicine. By using cutting- edge diagnostic tests, we'll be able to customize an individual's cancer treatment," said Joseph Sparano, M.D., Montefiore Medical Center, Bronx, NY, and Eastern Cooperative Oncology Group protocol chair.

Women in the study will have a physical exam performed by their doctor every three to six months for the first five years, then once a year after that for up to 20 years. An annual mammogram will check for signs of recurrence.

For eligibility and registration information regarding TAILORx, go to http://www.ctsu.org/ and enter "TAILORx" in the search box.

To view the PDQ summary of the TAILORx protocol, including contact information for sites currently enrolling participants, please go to http://www.cancer.gov/clinicaltrials/ECOG-PACCT-1.



###


*NCI-Sponsored Clinical Trials Groups: Eastern Cooperative Oncology Group (ECOG), North Central Cancer Treatment Group (NCCTG), The Southwest Oncology Group (SWOG), Cancer and Acute Leukemia Group B (CALGB), American College of Surgeons Oncology Group (ACOSOG), National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), and National Surgical Adjuvant Breast and Bowel Project (NSABP).

**Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, Cronin M, Baehner R, Watson D, Bryant J, Costantino JP, Geyer CE, Wickerham DL, and Wolmark N. Gene Expression and Benefit of Chemotherapy in Women with Node Negative, Estrogen Receptor Positive Breast Cancer, JCO, online May 23, 2006.





"Toward Personalized Medicine," a National Cancer Institute-sponsored Science Writers' Seminar to launch TAILORx, will be held on May 23, 2006, on the NIH campus from 10:30 a.m. until 12:45 p.m. To register, please call (301) 496-6641.

To view a Q&A on TAILORx, go to http://www.cancer.gov/newscenter/pressreleases/TAILORxQandA.

For a complete set of links and other information related to TAILORx, go to http://www.cancer.gov/clinicaltrials/digestpage/TAILORx.

For more information about the NCI-sponsored clinical trials groups, please visit:
http://www.ecog.org
http://ncctg.mayo.edu
http://www.swog.org
http://www.calgb.org
http://www.acosog.org
http://www.nsabp.pitt.edu
National Cancer Institute of Canada Clinical Trials Group: www.ctg.queensu.ca

For more information about cancer, please visit the NCI Web site at http://www.cancer.gov, or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
Cathya is offline   Reply With Quote
Old 05-27-2006, 08:48 PM   #2
Cathya
Senior Member
 
Cathya's Avatar
 
Join Date: Sep 2005
Location: Ontario, Canada
Posts: 752
Cancer Diagnostics: Informing the Development of Tailored Cancer Therapy


Reported by Dorie Hightower
May 23, 2006


Advances in genetic research are transforming cancer diagnosis, and treatments that are tailored to the specific molecular changes that drive tumor growth are now being developed. Because most cancers result from several genetic mutations, NCI is focusing on developing diagnostic tests that identify a number of genetic markers that can be used to predict a person's response to specific therapies and inform treatment decisions for these diseases.

BenchMarks discussed those new diagnostic tools with Sheila E. Taube, Ph.D., director of the Cancer Diagnosis Program (CDP) for NCI’s Division of Cancer Treatment and Diagnosis. The Cancer Diagnosis Program is developing new tests using information from the human genome program and powerful new molecular technologies to individualize cancer treatment.

How do clinicians currently make treatment decisions for breast cancer?

In early stage invasive breast cancer, the most important issue is the likelihood of recurrence. The evaluation of the likelihood of recurrence is based on multiple factors, such as nodal status, tumor size, tumor grade, and ER (estrogen receptor), PR (progesterone receptor), and HER2 status, as well as the age of the patient. Currently, treatment decisions are based on the outcomes of many clinical trials, and on observations of large populations, which provide population-based probabilities of recurrence, but not an individual’s own risk. However, there is a significant unmet need: the ability to provide patients with quantitative, clinically validated predictors of the risk disease recurrence in the individual. Such information can help the patient make the best breast cancer treatment decisions.

How would the OncotypeDX™ improve decision making?

Oncotype DX™ is a tool that quantifies the likelihood of disease recurrence in women with early stage breast cancer and assesses the likely benefit from certain types of chemotherapy. With this information, it may be possible for doctors and patients to make more informed decisions about breast cancer treatment options. The test analyzes a specific set of genes within a tumor to determine a Recurrence Score™--a number between 0 and 100 that corresponds to a specific likelihood of breast cancer recurrence within 10 years of the initial diagnosis. The test has been extensively evaluated on tumor samples from patients where the outcome is known, and the predictive ability for an individual appears to be quite consistent.

Would the Oncotype DX™ substitute for all of those factors, such as the tumor size and the patient’s history and age?

Yes, for early-stage, node-negative and hormone-receptor positive breast cancers. Along with staging, grading and other tumor marker analyses, Oncotype DX™ can provide greater insight into the likelihood of disease recurrence. The quantitative assessment that this test offers is important in weighing the benefits vs. the risks of adjuvant chemotherapy, and helps to determine the most appropriate treatment strategy – tailored to the individual patient.

What is the TAILORx trial?

The Trial Assigning IndividuaLized Options for Treatment (Rx) – TAILORx -- will focus on a molecular signature to determine the most effective cancer treatment, with the fewest side effects, for women with early-stage breast cancer. Using the Oncotype DX™ assay, a diagnostic test developed by Genomic Health, Inc., in collaboration with the National Surgical Adjuvant Breast and Bowel Project (NSABP), a network of cancer research professionals, TAILORx will attempt to determine the most appropriate therapy via this molecular test. If successful, patients with breast cancer will no longer receive all available systemic treatments when they are not necessary, but instead get the treatment that is best for them on an individual basis.

What is meant by over-treatment?

Adjuvant therapy for cancer is intended to reduce the risk of recurrence by eliminating malignant cells that may remain in the body after surgical removal of the primary tumor. The current guidelines recommend adjuvant chemotherapy for about 90 percent of women who fall into the category of node-negative, hormone-receptor positive early breast cancer. But we now know that about 70 percent of those patients will be alive and free of disease 15 years after treatment, with surgery alone--or lumpectomy followed by radiation. And if you add tamoxifen, a hormonal therapy, the outcome is even better. The problem has been that we have not been able to identify the 15-30 percent of patients who will recur, so we end up treating women who probably would not have a recurrence. That unnecessary exposure to the toxicities of chemotherapy is what we mean by “over-treatment”.

What is the downside of having chemotherapy?

One always has to weigh the benefits against the risks. There is a small rate of second cancers that are caused by chemo. If the risk of a second cancer is 1 or 2 percent, but the risk of recurrence is 30 percent, a patient still may choose to have the chemotherapy. There’s also some question about long-term effects on cognition caused by chemo; there can be cardiac problems; and with the addition of taxane drugs there can be nerve damage. Also, chemo often causes people to temporarily lose their hair and experience nausea and vomiting during treatment.

What is unique about Genomic Health’s process and why is it considered a step forward?

Most of the tests for expression of genes in a tumor were initially based on evaluation of frozen tumor material, so the ability to take formalin-fixed tissue (the form of tissue most commonly available), where the nucleic acid is damaged, and still get reproducible results, was a real step forward. Genomic Health’s approach is now being picked up by many of the companies who are involved in developing diagnostic tests.

What are some of the problems faced when moving new diagnostic tools into clinical use?

There are many steps along the way, and a lot of things that need to be assessed. There is the actual reproducibility of an assay--if you do it on Monday and you do it again on Tuesday, will you get the same result? There’s the standardization, reproducibility and robustness of the assay. But there’s also the harder question--does it give you clinically useful information? Tests can be reproducible but not help the patient and physician choose the best treatment options. An example is measurement of some serum markers such as carcinoembryonic antigen (CEA) to monitor for disease recurrence. The test is reproducible but does not provide specific enough information about whether there is disease recurrence to guide treatment – it can be positive for reasons other that cancer or negative if there is very little cancer present.

What is the difference between tests that are prognostic vs. those that are predictive?

Prognostic means the course of the disease in the absence of treatment. It tells you the likelihood of a patient’s disease being aggressive or non-aggressive. So then a doctor decides, based on that, I’m going to intervene, I’m going to treat the patient in a particular way. A predictive test helps you define what treatments are most likely to be effective.

For example, the initial observation of HER2 overexpression was that it seemed to be associated with poor prognosis--with worse outcomes for patients. Ultimately, the HER2 test was not a very strong prognostic indicator, particularly in node-negative breast cancer. Nodal status turned out to be a stronger indicator but HER2 was able to tell you within node-positive disease which patients were more likely to benefit from additional treatment. So, when we then wanted to use HER2 to predict the response to Herceptin, the characteristics of the assay had to be changed. It was difficult to take the test that had been used initially, and scale it up to a test that could be used broadly in many hands. One of the challenges in developing diagnostics is that we often begin analyzing the diagnostic in a context that’s different from the way we want to use it in the end.

How are these tests developed?

Developing these tests is an iterative process. You start out perhaps focusing on your standardization, and you have a proposed clinical use, and you measure the ‘marker’ in that context. And then, if the assay performs well, that is, reproducibly, but you want to change the clinical use, you have to go back and adjust the assay to make sure it can inform the decision you want to make. You always have to retest. You have to go through these loops a number of times until you finally go to a prospective trial.

So that’s what TAILORx is going to do?

That’s what TAILORx is going to do. The OncotypeDX™ was evaluated in an appropriately designed prospective/retrospective trial, in that a set of samples that were taken in a prospective way in the context of a clinical treatment trial but analyzed retrospectively, at the end of the trial. This way they did not have to start from scratch, because having the outcomes on those samples allowed the test to be evaluated without waiting many years for the trial to mature. That’s why we have the clinical trials groups collecting specimens on their trials so that we can then go back and ask questions about diagnostics in the context of a full set of specimens. The reason that OncotypeDX™ is as powerful as it appears to be is that the developers had access to specimens from clinical trials where the patients had been treated uniformly, and where there was good follow-up. So they were able to take these specimens and look at the relationship between the score on the test and the outcome. The OncotypeDX™ was clearly demonstrated to provide a reproducible estimate of the risk of recurrence. TAILORx will allow us to determine whether OncotypeDX™ can also accurately predict which patients will benefit from the addition of chemotherapy to hormonal therapy. It was not possible to evaluate this question for women with recurrence scores in the intermediate range because there were not enough samples from the previous trials.

How much does the OncotypeDX™ cost compared to a mammogram?

The OncotypeDX™ costs a patient about $3,450, if there is no insurance reimbursement. A mammogram costs somewhere in the range of $100-200, but tests such as mammography, PSA screening and pap tests are screening tests. And if an abnormality is found in a screening test, that may lead to additional screening and biopsies, which all cost money.

It’s important to point out that there is a difference between a screening test and one that is performed once a diagnosis has been made. The OncotypeDX™ test has the potential for actually saving money for the healthcare system, because it may reduce the number of women who receive chemotherapy, which can cost $20,000 and more per patient.

What are some of the other treatment issues your program is working on?

We’re looking at a similar problem to the breast cancer and chemotherapy issue with early stage colon cancer, but in this case, patients typically do not get adjuvant chemotherapy after surgery, and some patients and physicians believe that they are being under-treated. So there is a need for a test that identifies those patients who will benefit from the addition of chemotherapy.

What is NCI doing to help bring new diagnostic tools into clinical practice?

We meet with companies to try to focus their efforts, and if they have a potentially useful technology, we help them determine what the clinical questions are, and where the technology might be of greatest use. We begin by focusing on the clinical problem, rather than on the technology or the assay, which is a change in the way assay development has been done in the past, where mostly people develop a test based on some interesting biology, and then they look for a place to use it. Our program is saying, let’s home in on a clinical problem and figure out what technologies or markers are available.

###
Cathya is offline   Reply With Quote
Reply

Thread Tools
Display Modes

Posting Rules
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts

BB code is On
Smilies are On
[IMG] code is On
HTML code is Off

Forum Jump


All times are GMT -7. The time now is 02:54 AM.


Powered by vBulletin® Version 3.8.7
Copyright ©2000 - 2024, vBulletin Solutions, Inc.
Copyright HER2 Support Group 2007 - 2021
free webpage hit counter