NEW ORLEANS — A genomic test can help predict which patients with early-stage breast cancer will derive the most benefit from adjuvant chemotherapy, according to the initial results of the randomized phase 3 MINDACT trial presented at the American Association for Cancer Research Annual Meeting.
The findings could “de-escalate the use of adjuvant chemotherapy and spare many patients an aggressive treatment they will not benefit from,” said researcher Martine Piccart, MD, PhD, head of the medicine department at Jules Bordet Institute in Belgium and co-founder and chair of the Breast International Group.
Advanced breast cancer is largely an incurable disease. Consequently, oncologists prescribe adjuvant therapies to many women with early-stage disease in hopes of eradicating micrometastases.
However, adjuvant treatment particularly adjuvant chemotherapy is associated with long-term risks, so the potential survival benefit must be balanced with the potential for long-term risks such as secondary cancers, cardiac toxicity and reduced cognitive function, Piccart said.
The MINDACT trial the first prospective randomized controlled trial of a breast cancer recurrence genomic assay with level 1A clinical evidence compared the 70-gene signature MammaPrint (Agendia) with traditional clinical assessments to determine which patients with early-stage breast cancer could safely forego adjuvant chemotherapy.
The trial conducted at 111 centers in nine European countries included 6,693 women (median age, 55 years) who underwent surgery for early-stage breast cancer from 2007 to 2011. The majority had stage T1 (58%), node-negative (80%), hormone receptor-positive (88%), HER-2–negative (90%) disease.
Researchers evaluated study participants’ risk for tumor recurrence through MammaPrint analysis of tumor tissue, as well as through use of the Adjuvant! Online tool, which calculates recurrence risk based on common clinical and biological criteria.
The 2,745 study participants deemed at low risk for recurrence by both risk-assessment methods received no adjuvant chemotherapy.
The 1,806 participants categorized at high risk for recurrence by both methods received adjuvant chemotherapy.
The remaining 2,142 participants determined to have a high recurrence risk by one assessment method but at low recurrence risk by the other method were randomly assigned to adjuvant chemotherapy or no adjuvant chemotherapy.
Patients with hormone receptor-positive disease were eligible for adjuvant hormone therapy and could participate in a randomization that involved two endocrine therapy regimens.
Piccart and colleagues hypothesized that MammaPrint would outperform common clinical and biological criteria by reducing the prescription of adjuvant chemotherapy without compromising outcomes.
Researchers determined a 92% threshold for predicted 10-year OS without adjuvant chemotherapy using Adjuvant! Online criteria would be adequate.
After median follow-up of 5 years, 5.4% of women either died or experienced distant relapse.
Piccart and colleagues reported 5-year distant metastasis-free survival rates of 97.6% among women classified by both MammaPrint and Adjuvant! Online as having a low risk for recurrence, and 90.6% among those classified by both assessment methods as having a high risk for recurrence. Five-year distant metastasis-free survival among women for whom the two assessment methods yielded discordant recurrence risks had 5-year distant metastasis-free survival around 95%.
The primary statistical test in the analysis focused on women who were determined to be at low risk for recurrence by MammaPrint and high risk for recurrence by Adjuvant! Online who subsequently were randomly assigned to no adjuvant chemotherapy. This test was designed to establish trust in the MammaPrint genomic assay.
In this subgroup, researchers reported a 5-year distant metastasis-free survival rate of 94.7% (95% CI, 92.5-96.2).
The trial was not powered to answer the question of whether adjuvant chemotherapy benefits women with discordant risk assessments, Piccart said. However, an intent-to-treat analysis showed little separation in distant metastasis-free survival curves in these groups based on chemotherapy receipt.
“A statistician will tell you ... it is not totally impossible that there is a very small chemotherapy benefit,” Piccart said. “However, the relative reduction in risk ... would translate to a very small absolute benefit that would not justify the risks of chemotherapy.”
In the entire study population, use of the MammaPrint assay was associated with a 14% reduction in chemotherapy prescription vs. a clinical assessment.
Use of the assay was associated with a 46% reduction in chemotherapy prescriptions among patients determined to be at clinically high risk for breast cancer.
“This trial has played a major educational role ... and popularized the concept of biology-driven treatment,” Piccart said. “It demonstrated that genomics can provide important information in order to treat patients with early breast cancer in a more optimal way.” – by Mark Leiser
Piccart M, et al. Abstract CT-039. Presented at: American Association for Cancer Research Annual Meeting; April 16-20, 2016; New Orleans.
Piccart reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.