MINDACT points to differential breast cancer chemotherapy benefit by age
medwireNews: Exploratory data from the MINDACT trial suggest that women older than 50 years who have high clinical risk but low genomic risk according to the 70-gene MammaPrint signature may be able to forgo adjuvant chemotherapy for early-stage breast cancer.
By contrast, “in younger women, a potentially clinically relevant chemotherapy benefit of about 5 percentage points is observed at longer follow-up,” say the investigators.
While noting that this finding mirrors results from the TAILORx trial, they stress that “this subgroup analysis was exploratory, limited to the 1358 women at high clinical and low genomic risk with hormone receptor-positive, HER2-negative tumours.”.
The phase 3 MINDACT study enrolled 6693 patients with nonmetastatic, clinical stage T1, T2, or operable T3 breast cancer, and up to three positive lymph nodes. Adjuvant chemotherapy was given to participants classified as high risk both clinically and genomically – as assessed by a modified version of the Adjuvant! Online tool and MammaPrint, respectively – and withheld from those classed as low risk by both approaches.
Participants with discordant clinical and genomic risk were randomly assigned to receive adjuvant chemotherapy or not, with the intention-to-treat (ITT) population comprising all women with high clinical and low genomic risk (n=1497) and the primary test population comprising the subgroup of these patients who were not given chemotherapy (n=644).
After a median follow-up of 8.7 years, the 5-year distant metastasis-free survival (DMFS) rate in the primary test population was 95.1%, and the 95% confidence interval excluded the predefined noninferiority boundary of 92.0%, “supporting the previous analysis and proving MINDACT as a positive de-escalation trial,” say Martine Piccart (Institute Jules Bordet, Brussels, Belgium) and co-researchers.
In the ITT population, the DMFS rate at 8 years was 92.0% for patients who received adjuvant chemotherapy and 89.4% for those who did not, equating to an absolute difference of 2.6 percentage points favoring the use of chemotherapy and a significant hazard ratio (HR) of 0.66.
However, a prespecified exploratory analysis restricted to ITT participants with hormone receptor-positive, HER2-negative disease suggested that the benefit of chemotherapy may differ by age. Specifically, among women aged over 50 years, there was no difference in 8-year DMFS between those who did and did not receive chemotherapy, at rates of 90.2% and 90.0%, respectively.
But among those aged 50 years or younger, the 8-year DMFS rate was 93.6% with chemotherapy and 88.6% without, which gave an absolute difference of 5 percentage points in favor of chemotherapy and an adjusted significant HR of 0.54.
“For older women, a strong message from the mature results from MINDACT and TAILORx is that multigene signatures guiding omission of chemotherapy, in the presence of a high clinical risk, are robust decision aids,” write the investigators in The Lancet Oncology.
They continue: “The potential benefit of chemotherapy, given in addition to endocrine therapy, to younger women might be linked to chemotherapy-induced ovarian function suppression, although neither MINDACT nor TAILORx can confirm this hypothesis.
“These facts must be discussed in detail with every patient, as part of a shared decision-making process.”
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