Oncotype DX Trial: Some Breast Cancers Don't Need Chemo

Nick Mulcahy

September 28, 2015

Some women with early-stage breast cancer can skip chemotherapy without putting themselves at heightened risk for disease recurrence or spread at 5 years, according to new research.

The finding is important because it is from the first prospective evaluation of a widely used genetic test. Previous investigations of the popular 21-gene assay for breast cancer recurrence risk (Oncotype DX, Genomic Health) have been retrospective, so the evidence is less desirable.

In this study — known as TAILORx (Trial Assigning Individualised Options for Treatment) — the assay was used to determine which women had a low risk for recurrence and could therefore forgo chemotherapy and be treated with endocrine therapy alone.

Results were presented at the European Cancer Congress (ECC) 2015 in Vienna, and published online simultaneously in the New England Journal of Medicine.

The TAILORx study involved 10,253 women with hormone-receptor-positive, HER2-negative breast cancer and no disease spread to the lymph nodes. The women (15.9%) with a recurrence risk score condsidered low (range, 0 to 10) were eligible to receive an aromatase inhibitor, tamoxifen, or a combination of the two for 5 years — with no chemotherapy.

The women with intermediate and high recurrence risk scores were managed in the two other study groups. Those results are not yet available.

In the low-risk group, the rate of invasive disease-free survival at 5 years was 93.8% (95% confidence interval [CI], 92.4 - 94.9). The rate of freedom from recurrence at 5 years was 98.7% (95% CI, 97.9 - 99.2). And the rate of freedom from recurrence of breast cancer at a distant site (i.e., metastatic disease) was 99.3% (95% CI, 98.7 - 99.6), report Kathy Albain, MD, from Loyola University in Chicago, and colleagues.

In addition, there were 88 cases of either invasive cancer or death during the 5-year study period, and 30 deaths from other causes. The rate of overall survival at 5 years was 98.0% (95% CI, 97.1 - 98.6).

"There was outstanding survival with endocrine therapy alone. The test provides us with greater certainty of who can safely avoid chemotherapy," Dr Albain said in a press statement.

In regular clinical practice, all of the women in the study would have been candidates for chemotherapy, according to the National Comprehensive Cancer Network (NCCN) guidelines, because of their clinicopathologic features.

In an accompanying editorial, Clifford Hudis, MD, from the Memorial Sloan Kettering Cancer Center in New York City, says that "this result is numerically good enough to exclude any potentially meaningful benefit for additional chemotherapy," referring to the almost complete absence of metastatic spread at 5 years in the women who received endocrine therapy alone.

The results are a "confirmation" that the 21-gene assay, which has been used for about 10 years by clinicians, "can identify a cohort of patients who should be spared chemotherapy," writes Dr Hudis.

However, he adds, the TAILORx results are "both reassuring and frustrating."

Dr Hudis believes results from this and other prospective trials "cannot come soon enough," given the already "widespread adoption" of the assay by clinicians. But there is a problem, he says: the investigators changed the recurrence risk scoring scale for the study.

Dr Albain and her colleagues explain that because they wanted "to minimize the potential for undertreatment of the participants enrolled in our trial," they tightened the definitions of risk.

Thus, recurrence scores used in the TAILORx study are different than those generally applied in the widely used assay for low (≤10 vs <18), intermediate (11 to 25 vs 18 to 30), and high (≥26 vs ≥31) ranges.

Dr Hudis is worried about the changed low-risk definition. "For the many physicians already using the test, the gap between this cutoff point of 10 and the higher 'standard' cutoff point of 18 may be a concern."

There will be two conflicting guides.

And he anticipates trouble. "There will be two conflicting guides to their treatment that need to be reconciled: the cutoff point used in this trial and the previously available cutoff point that is associated with the commercial test," he explains.

But Dr Hudis suggests that the snafu is not overwhelming, in part, because it is likely that other multigene tests will also be proven to "provide a prediction of chemotherapy benefit."

Less expensive tests would be helpful, especially for global use, he says. The Oncotype DX is regularly cited as costing $4000.

More Study Details

The study authors provide some context for their study. In 2014, more than 100,000 women in the United States received a diagnosis of estrogen-receptor-positive breast cancer with negative axillary lymph nodes. It is well known that endocrine therapy is good enough treatment for most of these women.

"Although approximately 85% of these women may be recurrence-free at 10 years with adjuvant endocrine therapy alone, the addition of chemotherapy leads to a relative reduction in the risk of recurrence of approximately 30% on average, which translates into an absolute benefit in the rate of freedom from recurrence of up to 5 percentage points," they report.

Thus, the aim of the trial is to help define who can skip chemotherapy safely.

The women in TAILORx were 18 to 75 years of age, and all met the NCCN guideline recommendations for adjuvant chemotherapy (primary tumor size of 1.1 to 5.0 cm; or 0.6 to 1.0 cm for a tumor of intermediate or high histologic grade or nuclear grade, or both).

All low-risk patients were assigned to endocrine therapy alone. The 1730 (16.9%) high-risk patients — with a recurrence risk score of at least 26 — were assigned to chemotherapy plus endocrine therapy.

The 6897 (67.3%) patients with a midrange score of 11 to 25 were randomly assigned to chemotherapy plus endocrine therapy or to endocrine therapy alone.

In various news reports from the ECC, a number of clinicians pointed out that the intermediate-risk group is the most interesting and clinically important because of uncertainty about chemotherapy use. But those results are not yet available. Maybe they will be at next year's conference.

This study was sponsored by the National Cancer Institute, and was coordinated by the ECOG and subsequently the ECOG–ACRIN Cancer Research Group. Some of the study authors report financial ties to industry, including Genomic Health, the makers of the Oncotype DX test. Dr Hudis reprots receiving grant support from Genomic Health.

European Cancer Congress (ECC) 2015: Abstract 5BA. Presented September 28, 2015.


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