TAILORx: Gene expression assay helps spare adjuvant chemo in many breast cancer patients
Clinical use of a 21-gene expression assay can help spare adjuvant chemotherapy in many patients with early breast cancer, according to results of a large trial hailed by experts as practice-changing.
TAILORx, the largest breast cancer treatment trial ever conducted so far, included 10,253 eligible women with hormone receptor–positive, HER2-negative, axillary node–negative, early-stage breast cancer who underwent assessment with the Oncotype DX 21-gene breast cancer recurrence score assay. Among 6,711 patients (69 percent) with a midrange recurrence score of 11–25, for whom the benefit of adding chemotherapy to endocrine therapy had remained uncertain previously, results showed that endocrine therapy was noninferior to chemoendocrine therapy in the primary endpoint of invasive disease–free survival (iDFS). [Sparano JA, et al, ASCO 2018, abstract LBA1; N Engl J Med 2018, doi: 10.1056/NEJMoa1804710]
“This noninferiority trial met its primary endpoint,” said investigator Dr Joseph A. Sparano of the Montefiore Medical Center, New York, US. “At 9 years, iDFS rate was 83.3 percent in patients randomized to receive endocrine therapy vs 84.3 percent in those randomized to receive chemoendocrine therapy, with a hazard ratio of 1.08 [p=0.26].”
In addition, a similar proportion of patients in the endocrine therapy and chemoendocrine therapy groups were free from distant disease recurrence (94.5 percent vs 95 percent) or local-regional disease recurrence (92.2 percent vs 92.9 percent) at 9 years. The overall survival rates at 9 years were also similar between the two groups (93.9 percent vs 93.8 percent).
“An exploratory analysis showed that adding chemotherapy to endocrine therapy offered some benefit in patients aged 50 years or younger with a recurrence score of 16–25,” reported Sparano. “At 9 years, this approach resulted in a 1.6 percent reduction in distant recurrences in those with a recurrence score of 16–20, and a 6.5 percent reduction in those with a recurrence score of 21–25.”
In this US federally-sponsored trial, 1,619 patients (17 percent) had a recurrence score of ≤10. These patients were treated with endocrine therapy alone due to their low risk of recurrence. At 9 years, distant recurrence rate was 3 percent in this group.
The trial also included 1,389 patients (14 percent) with a recurrence score of ≥26, who were known to have poorer outcomes and higher event rates despite more aggressive treatment. In the trial, these patients had a 9-year distant recurrence rate of 13 percent despite treatment with chemoendocrine therapy.
“Based on our findings, adjuvant chemotherapy may be spared in all women older than 50 years of age with a midrange recurrence score of 11–25, and in 36 percent of women 50 years of age or younger with the same recurrence score. Patients 50 years of age or younger with a recurrence score of 16–25 may obtain some benefit from chemotherapy,” concluded Sparano.
“Application of the 21-gene expression assay in clinical practice in patients with hormone receptor–positive, HER2-negative, axillary node–negative, early-stage breast cancer could be estimated to spare chemotherapy in 69 percent of patients and to select chemotherapy in 31 percent of patients,” he added.
“These results are expected to be immediately practice-changing,” commented Dr Harold Burstein of the Dana-Farber Cancer Institute, Boston, Massachusetts, US, at an ASCO press conference. “The vast majority of women who undergo this test can be told with tremendous confidence and reassurance that they don’t need chemotherapy.”