Five-year AI Extension Increases Fracture Risk Without Reducing Breast Cancer Recurrence

Author: By Lynda Williams, Senior medwireNews Reporter

medwireNews: For postmenopausal women who have completed 5 years of endocrine therapy after treatment for early breast cancer, phase III study findings suggest that continuing aromatase inhibitor (AI) therapy for a further 2 years achieves equal improvement in survival to a 5-year extension while reducing the risk of fractures.

The SALSA trial participants had already completed 5 years of adjuvant tamoxifen and/or AI therapy after treatment for stage I–III invasive hormone receptor-positive breast cancer, explain Michael Gnant, from the Medical University of Vienna in Austria, and co-workers.

The majority of patients had T1 (72.8%) or T2 (25.0%) and N0 (66.9%) or N1 (30.8%) disease and most patients had not been given neoadjuvant chemotherapy (71.2%), they say.

The primary endpoint of disease-free survival was determined in women who were free from recurrence and continuing trial participation 2 years after being randomly assigned to receive anastrozole 1 mg/day for 2 years (n=1603) or 5 years (n=1605).

Ten years on from randomisation, the disease-free survival rate was a comparable 73.6% with the 2-year course and 73.9% with the 5-year course.

The secondary endpoint of the 10-year rate of overall survival from randomisation was also similar in the two groups, at 87.5% and 87.3%, respectively, as were the rates of contralateral breast cancer and secondary primary cancers.

The researchers note that approximately a fifth of patients had discontinued anastrozole by 2 years, rising to a third of the 5-year cohort by the end of the study period. But exploratory analysis adjusting for adherence continued to show similar survival outcomes in the two treatment arms.

Of concern, however, 6.3% of patients given a 5-year AI extension had sustained a clinical bone fracture in the 5 years after entering the study compared with 4.7% of those given the 2-year AI extension, giving a hazard ratio of 1.35 in favour of the shorter course, although this did not reach statistical significance.

“This difference in fracture risk occurred despite the equivalent use of bone-targeted medications in the two groups”, the researchers observe.

Adverse events (AEs) were as expected for anastrozole therapy, the team continues, with serious AEs related to anastrozole occurring in 2.3% and 4.0% of the 2-year and 5-year extension groups, respectively.

Writing in The New England Journal of Medicine, the investigators say that their study population “represents an average-risk group of postmenopausal women with breast cancer” and therefore “we cannot fully rule out a small benefit for the highest-risk patients.”

Nevertheless, they conclude that “the extension of aromatase-inhibitor therapy for 2 years rather than 5 years was sufficient to maximize the benefits of such therapy in most patients without extending the exposure to toxic effects.”

Discussing the findings in a linked editorial, Pamela Goodwin, from the University of Toronto in Ontario, Canada, says that “[d]ecisions regarding extended aromatase-inhibitor therapy will continue to be individualized, with a combined assessment of recurrence risk, treatment tolerance, and patient preference.”

Nevertheless, she emphasizes that the findings in a population of breast cancer patients “who are at low or average risk underscore the importance of avoiding iatrogenic complications when making these decisions.”

References

• Gnant M, Fitzal F, Rinnerthaler G, et al. Duration of adjuvant aromatase-inhibitor therapy in postmenopausal breast cancer. N Engl J Med 2021;385:395–405. DOI: 10.1056/NEJMoa2104162
• Goodwin PJ. Extended aromatase inhibitors in hormone-receptor–positive breast cancer. N Engl J Med 2021;385:462–463. DOI: 10.1056/NEJMe2109356