No benefit of adjuvant metformin in HR-positive, negative early breast cancer
medwireNews: Adjuvant treatment with metformin does not improve the outcomes of patients with hormone receptor (HR)-positive or negative early breast cancer, suggest trial data presented at the 2021 San Antonio Breast Cancer Symposium.
“Metformin should not be used as breast cancer treatment” in these patients, the presenting author Pamela Goodwin (University of Toronto, Ontario, Canada) told delegates, but she drew attention to an exploratory analysis pointing to a possible benefit in those with HER2-positive disease.
Outlining the rationale for studying metformin, the presenter explained that the drug has been shown to reduce Ki67 levels in breast cancer cells and slow the growth of breast cancer in preclinical studies. “Furthermore, emerging evidence suggests that the use of metformin to treat diabetes in breast cancer patients may be associated with improved outcomes,” she added.
The CCTG MA.32 trial investigators therefore recruited 3649 nondiabetic patients with nonmetastatic breast cancer at moderate or high risk for recurrence after surgery with negative margins, and randomly assigned them to receive adjuvant metformin 850 mg twice daily or placebo for up to 5 years. Participants were stratified by HR status, HER2 status, BMI, and receipt of chemotherapy.
The primary analysis of the double-blind study was conducted in the HR-positive population (n=2533), and showed no significant difference in invasive disease-free survival (IDFS) between metformin- and placebo-treated participants. The proportions of patients experiencing an IDFS event were a comparable 18.5% and 18.3%, respectively.
There was also no significant improvement with the use of metformin versus placebo with regard to other endpoints, including overall survival (OS), distant DFS, and breast cancer-free interval.
The findings were similar in the HR-negative population (n=1116), confirming the results of an earlier interim analysis that showed no benefit of metformin in these patients and led to discontinuation of the study drug in these patients due to futility, said Goodwin.
However, treatment with metformin did appear to be associated with a significant improvement in IDFS and OS among a subgroup of 620 patients with HER2-positive disease, with hazard ratios of 0.64 and 0.53 relative to placebo.
The IDFS and OS advantage offered by metformin was especially prominent among participants harboring a at least one C allele of the rs11212617 single nucleotide polymorphism located close to the ATM gene (hazard ratios=0.51 and 0.35, respectively), highlighted Goodwin. But there was no benefit of metformin among those carrying a homozygous A allele.
The presenter cautioned, however, that “no p-value ‘spend’ was allocated to this comparison,” and therefore, “it requires replication in a prospective trial focusing on the HER2-positive population.”
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