The US National Cancer Institute has begun enrolling around 4,390 patients with breast cancer in a large prospective trial to test the ability of Genomic Health's Oncotype Dx assay to predict their response to chemotherapy.
The Trial Assigning Individualized Options for Treatment, or TAILORx, will be the first prospective study examining chemotherapy prediction with Oncotype, and it follows on the heels of a study associating the test's recurrence score with a likely benefit of chemotherapy.
Importantly for molecular diagnostics companies hoping to get into the breast cancer treatment-response market, TAILORx will also yield a repository of tissue and other specimens for use in future studies of diagnostics.
Genomic Health has been promoting its test as predictive of "certain types of chemotherapy," but the study, published in the online version of the Journal of Clinical Oncology, represents the first publication of data supporting this claim in a peer-reviewed journal.
The NCI last week announced the TAILORx study, which is coordinated by the Eastern Cooperative Oncology Group, on the same day that the JCO published retrospective findings linking Oncotype's recurrence score to chemotherapy benefit in patients with node-negative, estrogen-receptor positive breast cancer. The study provided the experimental relationships between high- and low-recurrence score and chemotherapy response for TAILORx to investigate further, according to the NCI.
"The TAILORx design basically is saying that the [Genomic Health] assay really can be considered something that can be thought about as a routine test for ER-positive, node-negative women."
Although the chemotherapy-benefit article is the first such piece published, Genomic Health does not expect to make any changes to its marketing in the wake of the publication, according to a spokesperson. Genomic Health first presented its research linking recurrence scores to chemotherapy at the December 2004 San Antonio Breast Cancer Symposium.
Oncotype recurrence scores are aimed to predict an individual's chance of distant breast cancer recurrence, with a higher score indicating higher probability of recurrence, while lower scores suggest lower chances. In studies of chemotherapy response, the same recurrence score is compared against chemotherapy response rates. TAILORx is designed to explore the gray area between treatment options chosen for patients who receive either a high (above 25) or a low (below 11) Oncotype recurrence score.
"In between those two, we don't know when the chemotherapy benefit begins to go away, or how much is in there," Charles Geyer, director of medical affairs at the US National Surgical Adjuvant Breast and Bowel Project, said this week in an interview with Pharmacogenomics Reporter. This group of about 4,390 patients will be randomly assigned to chemotherapy plus hormone therapy or hormone therapy alone.
Patients who receive a high recurrence score will be treated with chemotherapy and hormone therapy, while low-scoring patients will receive hormone therapy alone.
The TAILORx study's clinical trials groups will likely have to test between 10,000 and 11,000 women to enroll enough who both agree to randomized therapy and whose Oncotype score is between 10 and 26, said Geyer.
Although the trial will focus on mid-range scoring patients, researchers will ask high- and low-scoring patients to donate tumor samples because new hormonal therapies have emerged since the previous Oncotype research was conducted. "With a new hormonal therapy, what kind of data will the assay generate?" Geyer asked. "So, those things will be studied as well."
No control groups will be used for tumor samples at the high and low ends of the recurrence score because patients in those groups will be receiving the current standard of care. "The TAILORx design basically is saying that the [Genomic Health] assay really can be considered something that can be thought about as a routine test for ER-positive, node-negative women," said Geyer.
The clinical trials groups involved in TAILORx are: the Eastern Cooperative Oncology Group; North Central Cancer Treatment Group; The Southwest Oncology Group; Cancer and Acute Leukemia Group B; American College of Surgeons Oncology Group; National Cancer Institute of Canada Clinical Trials Group; and the National Surgical Adjuvant Breast and Bowel Project.
Patients participating in the trial will be asked to donate tissue to the US Cooperative Group's tumor bank "so that as new technologies become available that look like they might be an improvement on [Genomic Health's], there will be a place to go and evaluate these things more quickly," said Geyer. "These will be very precious resources. There clearly would be competition between industry and academic investigators for tissue."
Chemo Response and Oncotype Highs and Lows
Though the research published in last week's online JCO is not new, the journal's peer review process confers an additional layer of credibility to a strong association between chemotherapy response and an Oncotype recurrence score.
However, real understanding of the test's value will come as a result of the TAILORx trial, said Charles Shapiro, director of breast medical oncology at Ohio State Medical Center and Comprehensive Cancer Center, in an interview this week. "I think that most people accept this data, and think it's real, but [the JCO's findings are based on] retrospective data generated on a trial that was old," he said. OSMC is participating in the TAILORx trial.
Shapiro said he uses Oncotype on patients in whom a chemotherapy risk-benefit picture is unclear. Although, he added, "if chemotherapy is unwarranted considering the risk factors, I don't send an Oncotype assay, generally."
Publication in JCO "is what really gives the study its clinical value," said Geyer. Patients with a smaller recurrence score as assessed by Oncotype are at a significantly reduced risk of experiencing a return of their cancer, while the approximately one-quarter of patients with a high recurrence score have a roughly 40-percent chance of recurrence, he said. "If you give chemotherapy to those patients, they get a huge benefit — they get an absolute benefit of [about] 28 percent," he added.
In node-negative, estrogen receptor-positive breast cancer patients, the chances of remaining in remission are about 4 percent to 5 percent higher when chemotherapy is added to hormone therapy, Geyer said. But that result involves treating with chemotherapy the 80 percent to 85 percent of women who will not likely benefit, he said. "Most doctors, most patients will say, 'If we can move that number up 4 or 5 percent, then we'll go through that chemotherapy,'" said Geyer.
The clinical factors currently used to determine whether a patient should be treated with chemotherapy include tumor size, nodal status, and hormone-receptor status. "Without this tool, the tendency was to give chemotherapy to everybody with a 1-centimeter or greater tumor, irrespective of the nodal status," said Shapiro.
— Chris Womack ([email protected])