Tests Hold Promise for Tailoring Drugs to Cancer Patients, But Some See Risk
"A lab test that may help predict which chemotherapy drugs will work best in a patient has sparked controversy after a leading cancer panel ruled the tests aren't ready for routine use.
"The tests, known as chemo sensitivity and resistance assays, or CSRAs, have the potential to revolutionize cancer treatment by testing different chemotherapy drugs directly against a sample of the tumor to identify which is the most effective.
"Right now, chemo drugs are prescribed based on their overall performance in past clinical trials. But even the best drugs may fail to help between 30% and 60% of patients, depending on the disease. It's impossible to predict the outcome of a particular cancer treatment for any individual because every cancer is different."
<remainder of article redacted, out of respect for WSJ copyright>
The article quotes two oncologists who strongly support the utilization of CSRAs, two patients who derived major benefit from treatments identified by the tests, and a lead investigator from the American Society of Clinical Oncology, who opposes utilization of the tests in current oncology practice.
The ASCO panel reportedly said that cell-death endpoint tests weren't included in the review simply because there weren't any "reliable" studies assessing them. The article goes on to note that "sometimes the tests return the result that no treatment works. In that case, the patient may be advised to go to a clinical trial and not undergo standard therapy." The article went on to quote the co-chairperson on the ASCO panel, Deborah Schrag, oncologist at Memorial Sloan Kettering Cancer Center: "There is a potential for harm," says Dr. Schrag. "We think the concept is fabulous, but they have to be rigorously tested and they just haven't been."
The criticisms leveled against the assays by Dr. Schrag are, however, simply outrageous, and they illustrate the veracity of the criticisms of the ASCO panel which were made in the press release shown below. Simply stated, the panel was lacking in both knowledge and expertise.
Dr. Schrag says that the cell death assays weren't included because there were no reliable studies supporting them. This is an outrageously false statement, as there are more than 40 full publications in the peer-review medical literature, many appearing in top ranked journals, reporting correlations between assay results and treatment results in more than 2,000 patients. In every single study, patients treated with drugs active in the assays were much more likely to derive clinical benefit than were patients treated with drugs inactive in the assays, with the former group being 7 to 9 times more likely to benefit than the latter group. Numerous studies also showed that patients treated with CSRA-"active" drugs enjoyed significantly longer survivals than patients treated with CSRA-"negative" drugs. These data are completely consistent and without any controversy whatsoever. Because the ASCO panel contained no investigators with expertise in this area, and because the ASCO panel did not seek the input of investigators who had such expertise, they had no understanding of the vast literature which does exist to document the accuracy of the tests, and the major criteria always used to evaluate all laboratory tests is their accuracy.
The argument that there is a potential for "harm" is entirely specious. As is explained elsewhere on this website, there is only rarely a best " standard" therapy which has been proven to be the "best" treatment for a given situation. In the overwhelming majority of cases, there is a choice between several to a dozen different forms of treatment, all of which would have an equal chance of working (or failing to work) based on a flip of the coin. If an oncologist uses the tests to choose between forms of treatment with known equivalent probabilities of success, then patients will never be harmed, but will usually be helped.
The statement about being "deprived" of "standard" (meaning "best guess") therapy in favor of referral to a clinical trial is very misleading. Firstly, Memorial Sloan Kettering routinely refers for clinical trials (with vanishingly low success rates) patients for whom "standard" forms of therapy (with higher probabilities of success) can be identified through the use of the assays. Secondly, the only situations where the assays would be used to direct patients away from "standard" therapies (e.g. and onto clinical trials) are situations in which there is already a very low probability of success with standard treatments (75% of all the chemotherapy given in the USA provides no benefit, but often inflicts serious toxicity), and where simple "supportive care" (i.e. no chemotherapy) would be considered to be an equally valid treatment option prior to performance of the test. No one would "deny" potentially curative treatment to a cancer patient solely on the basis of a CSRA failing to identify a promising drug or drugs. Rather, the situation in which a patient might be directed to a clinical trial is one in which the situation already appears to be hopeless (e.g. the patient has already failed to benefit from the "standard" treatments), and the test is ordered as a last-ditch effort to see if a particularly active drug or drugs can be identified before resorting to either a clinical trial or to "supportive care."
The American Society of Clinical Oncology has worked hard to promote the image that modern oncology offers highly effective treatments which have been validated and proven in rigorous clinical trials. This is a gross mischaracterization of fact. The median survival of a breast cancer patient with metastatic disease was 2 years in the year 1970 and it is still 2 years today. Thirty years of clinical trials in ovarian cancer have produced no significant findings, other than to confirm the therapeutic equivalency of cisplatin and carboplatin. etc., etc., etc. I call attention to the most excellent and well-researched article published in the March 22, 2004 issue of Fortune.
Please understand that I am in no way criticizing the WSJ story, which, under the circumstances, was very well done. Rather I am truly enraged at the way the academic oncology has worked so much harder to benefit itself, rather than to benefit its patients. In the process, academic clinical oncology has failed its patients, as explained so correctly in the Fortune Magazine article (such an article could only have come from outside the oncology literature, as it was an indictment of academic oncology community as a whole).
- Larry Weisenthal September 14, 2004