Cancer care – more tailored and more targeted.

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one size does not fit all

Cancer care is becoming more tailored and more targeted.  By Sarah Peters

Personalized medicine is more than just a catchy phrase. By matching treatment to the specific characteristics of the person and the cancer, personalized medicine helps people receive the care that’s right for them.

Each cancer is driven by its own set of underlying biological factors. This means that a treatment that works for one person may not work for another. For a growing number of cancer types, however, it has become possible to evaluate important characteristics of the cancer before treatment begins. In the case of breast cancer, for example, testing the tumor for overexpression of a protein known as HER2 provides information about whether HER2-targeted drugs such as Herceptin® (trastuzumab) are likely to be effective.

The number of new tests and treatments has expanded rapidly as our understanding of the biological basis of cancer increases. Several of these tests have already been incorporated into routine clinical practice, and many others are in development. To illustrate the breadth of this field, this article provides an overview of two quite different tests: Oncotype DX® and TumorGrafts™. The article also discusses Zevalin® (ibritumomab tiuxetan)—an innovative type of targeted therapy.

 

Oncotype DX Breast and Colon Cancer Tests

Gene expression profiling explores the patterns of genes that are active in tumor cells. Studies have demonstrated that gene expression provides important information about prognosis or likely response to treatment in several types of cancer. The Oncotype DX tests are genomic assays that evaluate the activity of certain genes in samples of breast or colon cancers.

The Oncotype DX breast cancer test is well established and has been added to US medical guidelines for early-stage breast cancer. The test has been shown to predict the likelihood of cancer recurrence and the likelihood of chemotherapy benefit in women with early-stage, estrogen receptor–positive breast cancer that is treated with hormonal therapy. The test evaluates the activity of 21 genes from a sample of the cancer to determine the patient’s recurrence score. The higher the recurrence score, the higher the risk of cancer recurrence. Women with a high risk of recurrence tend to derive the most benefit from chemotherapy.1 A version of the test is also now available for women with breast ductal carcinoma in situ (DCIS).

The Oncotype DX colon cancer test became available in 2010. Originally developed for use in patients with Stage II colon cancer, it has now also been validated among patients with Stage III colon cancer.2 Once again evaluation of several genes within the tumor is used to estimate a patient’s risk of cancer recurrence.

 

TumorGrafts

The TumorGraft process is not yet part of routine cancer care, but early evidence is promising and further studies to evaluate its effectiveness are under way. With this approach, samples of a patient’s tumor are implanted into mice; drugs are then tested in the mice to determine which are most likely to be effective in the patient.

Keren Paz, PhD, vice president of scientific innovation at Champions Oncology, explains: “We obtain the patient’s tumor and we implant it into mice to re-create the living and growing tumor; we then use this model as a personalized tool that closely mimics the disease in the patient. We wait for the tumor to grow in the mouse, and as soon as it reaches a certain size we harvest the original tumor, cut it into small pieces, and reimplant it in a larger cohort of mice. Once these tumors are big enough, we divide those mice into groups, so in a way we have a nice army of mice. We treat each group with a drug or drug combination that is chosen in consultation with the patient’s medical oncologist. For each group we report the effect of the proposed chemotherapy to the medical oncologist. If the results show tumor shrinkage or stable disease, there is a very high likelihood that it will be an effective treatment. If the tumor continues to grow despite chemotherapy, it will not be an effective regimen for the patient, as well.”

A limitation of the test is that it takes an average of three months to get an answer from the mouse tests. As a result, the TumorGraft approach is not used to guide a patient’s first line of therapy. Answers provided by the TumorGraft, however, can help guide subsequent lines of treatment if those prove to be necessary. “We’re always hoping the patient is not going to need our services because we wish for him to remain disease-free,” says Dr. Paz, “but we will be there for them, ready with the information that can guide their second line of therapy.” The value of the TumorGraft technology, adds Dr. Paz, is its high level of accuracy, which translates into clinical benefit.

“Dr. K” was diagnosed with metastatic colorectal cancer in her late forties. A physician herself, she learned of Champions Oncology and the test from her oncologist in one of the world’s leading cancer institutes. The first attempt at getting the tumor to implant in the mice didn’t work, but the second attempt did. While waiting for the results, Dr. K was receiving chemotherapy that didn’t appear to be working; blood levels of a tumor marker known as carcinoembryonic antigen (CEA) were increasing. When the mice results came back, the chemotherapy was changed accordingly and her CEA levels began to decrease. She was unlikely to receive this treatment without the TumorGraft results.

“I find it fascinating that I can do this,” says Dr. K, noting that one of the potential benefits of the TumorGraft technology is avoiding the side effects of treatments that are unlikely to be effective. Treatments can be tested on the mice and not on the patient. She also finds it reassuring that if she needs additional lines of treatment in the future, results from the mice will be available: “In case this chemo doesn’t do as well, they already have three or four other options being tried on the mice right now. It gives you hope because you know that if something doesn’t work, they are already testing other things.”

 

Zevalin

The move toward more-individualized care is accompanied by a move toward more-targeted cancer treatment. Targeted therapies hone in on very specific characteristics of cancer cells. The development of targeted therapies for chronic myeloid leukemia, for example, has dramatically changed the treatment of that disease. Drugs such as Gleevec® (imatinib), Sprycel® (dasatinib), and Tasigna® (nilotinib) inhibit a protein that contributes to chronic myeloid leukemia and certain other types of cancer.

Zevalin is a type of targeted therapy known as radioimmunotherapy (RIT). RIT combines a monoclonal antibody—a type of protein that recognizes and binds to certain parts of cancer cells—with radioactive material. When the monoclonal antibody binds to the cancer cell, the radiation kills the cell.

Zevalin therapy combines the monoclonal antibody Rituxan® (rituximab) with Zevalin, which comprises an anti-CD20 monoclonal antibody and yttrium-90, a radioisotope that delivers the radiation. When injected into the body, Zevalin attaches to a protein (CD20) found only on the surface of B-lymphocytes, such as cancerous B-cells found in many forms of non-Hodgkin’s lymphoma (NHL). The radioactivity that is spontaneously emitted targets the B-cell and destroys it. This approach protects healthy tissue.

Many studies have evaluated the safety and the efficacy of Zevalin among patients with B-cell NHL. For example, in a study of patients with CD20-positive, advanced follicular lymphoma, patients who achieved a complete or partial response after first-line induction treatment received either Zevalin or no further treatment. Zevalin improved progression-free survival: progression-free survival was 36.5 months among patients treated with Zevalin compared with 13.3 months among patients who received no further treatment.3

An advantage of this approach is that treatment can be completed in a relatively short time (less than 10 days).

 

Steady Progress

Though progress against cancer can seem frustratingly slow, important headway is being made. New drugs are being developed, and the use of existing drugs is being refined. When effective cancer treatments can be identified in advance—without exposing the patient to the side effects of treatments that don’t provide a benefit—it can improve cancer outcomes as well as the patient’s quality of life.  _

 

 

References

1. Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor–positive breast cancer. Journal of Clinical Oncology. 2006;24(23):3726-34.

2. O’Connell MJ, Lee M, Lopatin M, et al. Validation of the 12-gene colon cancer recurrence score result in NSABP C-07 as a predictor of recurrence in Stage II and III colon cancer patients treated with 5FU/LV (5FU) and 5FU/LV + oxaliplatin (5FU+Ox). Paper presented at: 48th Annual Meeting of the American Society of Clinical Oncology; June 1-5, 2012; Chicago, IL. Abstract 3512.

3. Morschhauser F, Radford J, Van Hoof A, et al. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. Journal of Clinical Oncology. 2008;26(32):5156-64. doi: 10.1200/JCO.2008.17.2015.