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TAILORx Trial Data Reinforces Oncotype DX Utility; Questions Remain on Middle Risk Group

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NEW YORK (GenomeWeb) — An analysis of a subset of results of the TAILORx trial, published this morning in the New England Journal of Medicine, has shown prospectively that the vast majority of women with early-stage breast cancer who receive a low-risk score from Genomic Health's Oncotype DX test remain disease-free after five years of hormonal therapy alone without added chemotherapy.

Sponsored by the National Cancer Institute, TAILORx enrolled 10,273 patients overall across 1,182 sites and major cancer centers in six countries, including Canada. Every patient in the trial was tested using Oncotype DX — which divides women, based on an analysis of the expression of 21 genes, into one of three risk categories: low, intermediate, and high.

In the trial, women with an Oncotype DX recurrence score (RS) of 10 or less received hormonal therapy alone; women with an RS greater than 25 were treated with hormonal therapy plus chemotherapy; while women with a mid-range RS from 11 to 25 — the primary study group — were randomized to receive hormonal therapy with or without chemotherapy.

Previous research has already established that women with early-stage breast cancer and a high RS benefit from the addition of chemotherapy to their treatment, while those with a low RS — 18 or less — don't appear to gain additional benefit and can be treated effectively with hormonal therapy alone, and the new data further support this.

But the central expectation of the TAILORx trial has been that it would elucidate the clinical value of the intermediate RS result, especially in light of studies that have shown some discrepancies between Oncotype DX's classification of patients as intermediate-RS and the results of competing breast cancer risk tests.

For example, studies looking at Agendia's Mammaprint and BluePrint, and Nanostring's Prosigna tests have each showed that the Oncotype DX intermediate RS group appears to be made up of different genomic categories of cancers according to these other testing strategies, which implies that the overall category of intermediate RS may be heterogeneous in its outcomes and potential need for adjuvant chemotherapy.

Without data on the ultimate outcomes of these patients, drawing a conclusion on what these discrepancies mean has been impossible. Unfortunately, the current analysis of TAILORx has not yet delivered the awaited outcomes data for the randomized intermediate RS subcohort that could help answer some of these questions. 

Steve Shak, chief scientific officer of Genomic Health, told GenomeWeb that this is because there simply haven't yet been enough recurrences or other events in this subset to exclude or confirm a benefit from chemotherapy.

"The data monitoring committee advised that [the researchers] need to continue to follow those patients and that they will inform them when that [intermediate RS] analysis can be done," he said. "The understanding … is that it's taking longer because the event rates are low, which would be great news for patients."

Despite the question of the intermediate RS group remaining open, the initial analysis of TAILORx has still yielded important data with clear implications for the low-risk recurrence score group.

Notably, among the 1,626 patients with an RS result between zero and 10, 99.3 percent had no distant recurrence at five years after treatment with hormonal therapy alone, regardless of whether they would have otherwise met accepted guidelines for the use of chemotherapy in addition to hormonal therapy based on their age, tumor size, or tumor grade.

More specifically, the rate of invasive disease-free survival was 93.8 percent after five years, the rate of recurrence-free survival was 99.3 percent, the rate of distant or local-regional recurrence-free survival was 98.7 percent, and the rate of overall survival was 98 percent for this group. 

Shak said that Genomic Health hopes the results may have an impact in aligning physician practice with the guidelines, which recommend patients with low RS be treated with hormonal therapy alone.

According to Genomic Health, its own data shows that more than 170,000 breast cancer patients have seen their treatment strategy changed based the Oncotype DX test, but Shak said that doesn't mean there aren't still instances where decisions are being made without the added evidence provided by a molecular test. 

"We would all like to believe that when tests or treatments are in guidelines, in clinical practice there will be a uniform approach to treatment but … for a variety of reasons, there may be many cases where the traditional anatomic factors are still driving a quick decision to use hormonal or chemotherapy without the evidence of the biology to provide better guidance," he said.

The release of longer term data has been important to the broad and uniform adoption of other healthcare strategies, like the use of statins, Shak added. "This is going to have the same impact [for Oncotype DX,]" he said. 

Additionally, he said, the new long-term TAILORx data also have value in creating peace of mind for early-stage cancer survivors.

"Our hope with precision medicine is that [by] moving away from one-size-fits-all treatment, we also move away from one-size-fits-all fear," he said.

For example, in the study, among 1,626 patients with low RS treated with hormonal therapy alone, there were 10 distant recurrences, but there were also 43 other cancers not related to the initial breast cancer, and 12 deaths due to other causes. 

"It is striking the degree to which it appears that with that low RS, your worry should be more about some of those other things that could happen just to anyone in life rather than the breast cancer you were originally diagnosed with," Shak said.

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