Presented this morning at the American Association of Cancer Research meetings in Denver, Colorado, is an interesting study by Daniel Von Hoff and associates of the Phoenix-based Translational Genomics Research Institute (TGen).
From the TGen press release:
66 patients were treated at 9 different U.S. medical centers. All of the patients had previously experienced growth of their tumors while undergoing as many as two to six prior cancer treatments, including conventional chemotherapy.
However, after molecular profiling identified precise targets, new treatments were administered that resulted in patients experiencing significant periods of time when there was no progression of their cancer.
“This clinical trial was unique because patients acted as their own control,” said Dr. Von Hoff. “We compared each patient’s progression-free survival, following treatment based on molecular profiling, to how their tumors progressed under their prior treatment regimens, before molecular profiling.”
In a significant number of patients, the targeted treatments provided significantly longer periods when tumors did not progress, or even shrunk, said Dr. Von Hoff, who also is a Medical Director of US Oncology and a former Director of the Arizona Cancer Center at the University of Arizona.
He said this clinical trial demonstrated the value of personalized medicine, in which treatments are prescribed based on an individual’s specific genetic makeup. The type of drugs, dosages, their delivery and other treatment aspects – all are based on each patient’s individual medical needs.
Among the patients, 27 percent had breast cancer, 17 percent had colorectal cancer, 8 percent had ovarian cancer and 48 percent had cancers that were classified as miscellaneous.
Patients experienced varying levels of improvement. Among those with breast cancer, the period of progression-free survival increased for 44 percent of patients; for colorectal, 36 percent of patients; for ovarian, 20 percent of patients; and for miscellaneous cancers the improvement was seen in 16 percent of patients.
The molecular profiling for this research study was performed by Caris Diagnostics (Caris Dx) in Phoenix.
These results are the first in a series of studies in support of Target Now™, a commercially-available oncology testing service offered exclusively by Caris Dx. Target Now uses cutting-edge molecular profiling techniques, including both DNA microarray and immunohistochemical (IHC) analysis, to provide individualized information about a patient’s tumor as an aid to the treating oncologist.
The study was supported by a $5 million donation by a private philanthropist, apparently a cancer patient, as reported in the above press release.
This is a very interesting and innovative study design. It is very difficult (and horrendously expensive) to perform prospective, randomized trials. It is much simpler to use each patient as his/her own control, comparing results (progression-free survival) of the previous, empiric therapy with the “targeted” therapy. Even with the simplified design, however, this pilot study cost $5 million. The weaknesses are the often poor correlation of progression-free survival with overall survival and the subjectivity of “progression free survival” as a study endpoint.
Study details are eagerly awaited.
Edit April 20, 2009 16:13 GMT –>
The Von Hoff study abstract is now on American Association for Cancer Research Website.
Larry’s comments, based on data in study abstract:
Patients eligible had to have (1) clear disease progression on prior therapy and (2) received at least two prior lines of systemic chemotherapy. “Success” was defined as a time to progression (TTP) of at least 30% longer than the TTP of the most immediate prior therapy. A total of 18 patients (of 66) achieved this 30% improvement in time to progression.
An interesting question is what percentage of cancer patients in general have increased times to progression with subsequent cycles of empiric chemotherapy, compared to the prior empiric therapy. As I write this, I don’t know if there are any published data on this. If anyone is aware of whether or not these data exist, I’d appreciate knowing about it. Either respond to this blog post (requires easy registration) or send me a private email: email@example.com. Thanks!
An additional issue is the precision with which time to progression (TTP) with prior therapy was measured. With prospective clinical trials, using TTP as the primary endpoint, there is generally a protocol to standardize follow-up, with physical examination, laboratory tests, and radiographic tests being performed as standardized intervals, so that comparisons of TTP are meaningful. There would appear to be a problem with utilizing “historical” TTP on patients enrolled from the general oncology community, in which there is no standardization regarding the methodology for determining disease progression or the intervals at which these measurements are taking place. Additionally, we don’t know, from what is presented in the abstract, whether or not there was “blinded” assessment of TTP by outside auditors, or whether “historical” TTP was assessed and reported by the referring oncologists who enrolled the patients onto the trial.