NEW YORK (GenomeWeb) – As the US market for genomics-based breast cancer recurrence testing becomes ever more competitive, companies are looking to gain an edge by demonstrating that their tests are better at predicting how patients fare over the long term and whether they will benefit from chemotherapy or can skip it.
While Genomic Health's Oncotype DX test, which analyzes expression of 21 genes, is the clear market leader, other players, like Agendia, are maneuvering to capture some of that space by pitting their tests against each other.
At last week's American Society of Clinical Oncology meeting in Chicago, Agendia presented an abstract showing that its 70-gene MammaPrint test was able to classify women as either high or low risk who had been found in an intermediate recurrence risk range by Oncotype DX.
Importantly, the firm said, the treating physicians chose to change the patients' treatment to match the results indicated by the MammaPrint test 76 percent of the time.
Bastiaan van der Baan, Agendia's vice president of clinical affairs, told GenomeWeb that Agendia performed the study to demonstrate that its test could better classify as either high or low risk women who scored in an intermediate risk range with Genomic Health's Onoctype DX test, which he sad was "not very informative," since it did not provide physicians with a clear idea of whether or not the patient could forgo chemotherapy.
However, Genomic Health's CSO Steven Shak countered that the intermediate range, which is between 18 and 31, does provide useful information, adding that a woman who scores 19 is very different from a woman who scores 29, and that the physician could use that score in conjunction with other clinical features to make decisions. He added that although Agendia's study "showed that the assays differed, the study was not designed to look at how the women did and what the outcomes were."
Agendia carried out its PROMIS trial, for prospective study of MammaPrint in breast cancer patients with an intermediate recurrence score, along with 58 other US institutions. The trial included 840 women with estrogen receptor positive, lymph node negative breast cancer who scored between an 18 and 31 on the Oncotype DX test, and were thus considered to be within an intermediate range for risk of recurrence.
The firm then surveyed the physicians on whether they intended to treat their patients with chemotherapy or not. Typically, patients with a score less than 18 are considered low risk and can forgo chemotherapy, while patients with scores of 31 or higher are considered high risk and are treated with chemotherapy, but it is less clear how they should be treated when they fall in the middle range.
Next, they ran the MammaPrint test, which looks at expression of 70 genes, and delivered those scores to the physicians. The MammaPrint test reports a dichotomous score of either low or high risk, rather than a range, and it called 466 women, or 55 percent, high risk and 374 women, or 45 percent, low risk. Then the researchers surveyed the treating physicians again to see how they planned to treat the patients.
After getting the MammaPrint results, physicians added chemotherapy to 36 percent of the patients deemed high risk and removed it from 29 percent of the patients deemed low risk.
Physician adherence to the 70-gene MammaPrint assay was "88 percent for high-risk patients and 91 percent for low-risk patients," van der Baan said. "That's a very high number for adherence."
Both Agendia and Genomic Health have published data surrounding the utility of their tests for identifying low-risk breast cancer patients who can forgo chemotherapy, and Agendia has secured US Food and Drug Administration 510(k) clearance for MammaPrint.
In April, Agendia published the results of its so-called MINDACT trial, a nearly 7,000-patient study, showing that around 95 percent of the patients who were deemed low risk by MammaPrint but high risk by the standard tool used for risk assessment survived for five years without their disease coming back and without chemotherapy. The study provided Agendia the highest level of evidence, level 1A clinical evidence, that enables the National Comprehensive Cancer Network to update guidelines.
Genomic Health, meantime, published results this week of a 40,000-patient registry-based trial in collaboration with the National Cancer Institute and the Surveillance, Epidemiology, and End Results program suggesting Oncotype DX could also identify low-risk patients who could take hormonal therapy without chemotherapy, adding to a study published last year in the New England Journal of Medicine yielding similar results.
Nonetheless, there are known differences between the two firms' tests, which are responsible, at least in part, for the discrepancies in their results. As previously reported, researchers have identified differences between the two tests that can be explained in part by the fact that the two assays were developed to answer slightly different questions.
The Oncotype DX assay was validated on known cancer-associated targets in women who were treated for five years with hormonal therapy. As such, the test does not score women as high risk who have markers that indicate they would benefit from hormonal therapy. By contrast, MammaPrint was validated in untreated women and solely uses targets that distinguish between women with better or worse outcomes.
Both companies contend that the differences confer advantages for their respective tests.
For instance, with regard to Agendia's PROMIS trial, Genomic Health's Shak said that the differences between the two tests could explain why some women scored as high risk on the MammaPrint assay, but received an intermediate score from Oncotype DX.
However, that high-risk MammaPrint score "is a concern," Shak said, because the MammaPrint test might be reporting a woman as high risk who just needs hormonal therapy, not necessarily chemotherapy.
Meanwhile, Agendia's van der Baan maintained that while being estrogen receptor positive or negative is a good marker for response to hormonal therapy, it is not as good a marker for recurrence, and as such, the MammaPrint assay is better off for being developed independently of ER status.
Thus far, however, there is no head-to-head outcomes data that demonstrates clearly whether one test is better than the other at predicting which women will benefit from chemotherapy. Van der Baan said that the company would not be able to get that data in the PROMIS trial because there were not enough women enrolled.