Test Identifies Patients Who Benefit From Targeted Drugs

Clinical study results published at the annual meeting of the American Society of Clinical Oncology (ASCO) show that a new laboratory test has accurately identified patients who would benefit from treatment with the molecularly-targeted anti-cancer therapies gefitinib (Iressa) and erlotinib (Tarceva).

The new test, called EGFRx (TM), predicted accurately for the survival of patients treated with the targeted drugs. The finding is important because the EGFRx (TM) test, which can also be applied to many emerging targeted cancer drugs, could help solve the growing problem of knowing which patients should receive costly, new treatments that can have harmful side-effects and which work for some but not all cancer patients who receive them. (The test can discriminate between the activity of different targeted drugs and identify situations in which it is advantageous to combine the targeted drugs with other types of cancer drugs

The new test relies upon what is called "Whole Cell Profiling" in which living tumor cells are removed from an individual cancer patient and exposed in the laboratory to the new drugs. A variety of metabolic and apoptotic measurements are then used to determine if a specific drug was successful at killing the patient's cancer cells. The whole cell profiling method differs from other tests in that it assesses the activity of a drug upon combined effect of all cellular processes, using combined metabolic and morphologic endpoints. Other tests, such as those which identify DNA or RNA sequences or expression of individual proteins often examine only one component of a much larger, interactive process.

The whole cell profiling method makes the statistically significant association between prospectively reported test results and patient survival. Using the EGFRx (TM) assay and the whole cell profiling method, can correlate test results which are obtained in the lab and reported to physicians prior to patient treatment, with significantly longer or shorter overall patient survival depending upon whether the drug was found to be effective or ineffective at killing the patient's tumor cells in the laboratory.

Patients prospectively identified as favorable candidates averaged 485 days of life after treatment with the targeted therapy drugs. In contrast, patients identified as unfavorable candidates for the drugs averaged 75 days survival after receiving the drugs. This compares to 76 days average survival among patients identified as unfavorable candidates and who did not receive a targeted therapy drug. Survival among patients identified as unfavorable candidates was similar regardless of whether or not they received the targeted drugs.

Over the past few years, researchers have put enormous efforts into genetic profiling as a way of predicting patient response to targeted therapies. However, not gene-based test as been described that can discriminate differing levels of anti-tumor activity occurring among different targeted therapy drugs. Nor can a gene-based test identify situations in which it is advantageous to combine a targeted drug with other types of cancer drugs.

There is a growing array of targeted drugs to choose from. Most patients today are treated not with a targeted therapy drug alone but rather with a combination of chemotherapy drugs. Therefore, the existing DNA and RNA tests do not reflect the way cancer medicine actually is practiced today.

These so-called "smart drugs" focus their effects on specific, identifiable processes occurring within cancer cells. The new drugs are highly promising in that they sometimes provide benefit to patients who have failed traditional therapies. However, they do not work for everyone, they often have unwanted side effects, and they are all extremely expensive. Patients, physicians, insurance carriers, and the FDA are all calling for the discovery of predictive tests that allow for rational and cost-effective use of these drugs.

The EGFRx assay holds the key to solving some of the problems confronting a healthcare system that is seeking ways to best allocate available resources while accomplishing the critical task of matching individual patients with the treatments most likely to benefit them. Not only is it an important predictive test, it is also a unique tool that can help to identify newer and better drugs, evaluate promising drug combinations, and serve as a "gold standard" correlative model with which to develop new DNA, RNA, and protein-based tests that better predict for drug activity.

Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 17117

http://www.weisenthal.org/asco_06_egfr_gefitinib_nsclc_weise

My sister is battling her 3rd reoccurence of urachal adencarcinoma. In this last 2 weeks, this is the 3rd time I have heard this described. I'm sensing that I should be looking into this further. Do you have any specifics on how I get her invovled with this.

Melissa

One way to get involved is to check with Cancer Treatment Centers of America. They have listed on their web site that they are involved with Drug Resistance Testing. That is a major improvement over the "trial and error" treatment of cancer. However, I do not know what kind of Drug Resistance Testing they are involved with. Conventionally, oncologists make therapeutic decisions on an empirical basis rather than by thorough evaluation of pathological features and/or drug sensitivity tests.

Although extreme drug resistance assays are excellent at drug "resistance," they cannot "accurately" predict for drug "sensivity." The extreme drug resistance assay is specifically designed to identify "inactive" drugs and should not be used to identify "active" drugs. It has a very high specificty for drug resistance. However, many effective drugs do not test in the extreme drug resistance range. It has a relatively low sensitivity.

It must be realized that these assays are complex procedures, fraught with the potential for error and misinterpretation. The result are only meaningful to the extent that the laboratory in question is experienced and diligent in its quality assurance pratices. A patient interested in this testing should not hesitate to ask specific questions and to require specific answers of the laboratories under consideration.

The extreme drug resistance assay is a rather simple, straightforward test, requiring only about 5 or so minutes per assay of physician/lab work. DISC, MTT, and ATP assays are more geared to identifying "active) drugs (drugs which will work, as opposed to drugs which won't work), and are a whole lot more labor intensive, requiring an average of 3 hours of physician/lab work.

Upgrading clinical therapy by using drug "sensitivity" assays can improve the conventional situation by allowing more drugs to be considered. Drug "sensitivity" tests support the idea that a marginal benefit in terms of overall survival is observed in cancer patients with normal prognoses, but there are marked survival benefits for cancer patients with poor prognoses.

The key to improving drug sensitivity tests is related to the number and types of drugs tested. The more anti-cancer drug types there are in the selective arsenal, the more likely the system is to prove beneficial. In order to acquire sufficient data, tumors should be tested with at least two assay endpoints, and most often three, for sensitivity tests in any one patient. On average, up to twenty drugs and combinations at two concentrations in three different assay systems, is an effective way to avoid false-positive or false-negative data. Careful choice of drug doses and administration intervals also improves outcomes.

Drug sensitivity assays do not harm patients in any way except in terms of cost. Every cancer patient should have his/her own unique chemotherapy trial based on consultation of pathogenic profiles and drug sensitivity testing data. Research and application of drug sensitivity assays are being encouraged by growing patient demands, scientific advances and medical ethics. Drug sensitivity tests are not a luxury but an absolute necessity, and a powerful strategy that cannot be overlooked.

Peruse this web site, and at the bottom of the site is a list of specialized laboratories in the United States. These labls will provide you and your physician with in depth information and research on the testing they provide. Tens of thousands of individual patient specimens are currently being submitted for testing by more than 1,000 clinical oncologists, surgeons and pathologists annually in the U.S.

http://www.weisenthal.org/

It is certainly each practitioner's prerogative to order these tests. It seems probable that a self-educated oncologist, genuinely on the cutting-edge would tend to be aggressive in actual treatment beyond mere rhetoric, and make use of running tests on the biopsy before slecting a chemotherapy option.