No Difference in Overall Survival with Shorter Extended AI Therapy

Michael Gnant, MD

Investigators with the Austria Breast and Colorectal Cancer Study Group announced today that years can safely be shaved off anastrozole (Arimidex) treatment without affecting disease-free survival (DFS) for women with postmenopausal hormone receptor (HR)-positive breast cancer.

Additionally, shorter treatment spans can significantly reduce bone fractures, a side effect of aromatase-inhibitor (AI) therapy.

Results from the ABCSG-16 phase III trial were presented at the 2017 San Antonio Breast Cancer Symposium held in San Antonio, Texas.

For years, oncologists have followed up initial AI therapy with extended therapy for up to 5 years. Michael Gnant, MD, director and chairman, Department of Surgery, Comprehensive Cancer Center, Medical University of Vienna, recommended that oncologists immediately incorporate the new findings into practice by significantly reducing the use of adjuvant AI therapy following initial treatment. “There is simply no rationale to keep most patients on extended AI for longer than 2 years,” said Gnant, the study’s lead author.

Investigators enrolled 3484 postmenopausal women with HR+ early stage breast cancer from February 2004 to June 2010. The patients, all of whom had undergone an initial 5 years of adjuvant endocrine treatment, were randomly assigned to 2 years (n = 377) or 5 years (n = 380) of extended adjuvant therapy. About 50% of the enrolled patients had been treated initially with tamoxifen (Soltamox), and the remainder with AI or any sequence of tamoxifen and AI. Median age was 64 years.

The primary endpoint of was DFS, and investigators observed little difference between the 2 groups. At 10 years from randomization, the DFS rates were 71.1% for the 2-year group versus 70.3% for the 5-year group (HR, 0.997; 95% CI, 0.86-1.15; P = .982).

As of June 30, 2016, 78% of women in both trial arms were alive without recurrence. Recurrence, relapse, or other DFS events were equally common in both groups (22%). Investigators said there was no significant difference in overall survival or time to contralateral breast cancer.

For women in the 5-year adjuvant therapy arm, 6.3% had experienced bone fractures after 5 years on extended AI. In the 2-year group, 4.7% had experienced fractures by the end of the 5-year cutoff (HR, 1.353; P = .053). There were 71 fractures in the 2-year patient group (n = 1556) versus 98 in the 5-year cohort (n = 1571). Investigators concluded that longer treatment with anastrozole may be a risk factor for fractures.

Other side-effect reductions were noted for the 2-year group, including a lower incidence of arthralgia.

Ten years following randomization, 85.3% of patients in the 2-year arm were alive versus 84.9% of those in the 5-year arm (HR 1.007; P = .947). There was no difference between an additional 2 and 5 years of anastrozole in terms of overall survival, time to contralateral breast cancer, and time to second primary cancer, all of which were secondary endpoints in the trial.

Some patients may still benefit from taking anastrozole for longer periods, Gnant cautioned. He added that future translational research using data and biomaterial from patients in the ABCSG-16 trial could be useful in identifying potential molecular factors that influence how patients respond to anastrozole.

Patients with HR-positive breast cancer bear a significant risk of relapse and so extended AI therapy has become the norm and remains necessary, Gnant said. “More than 50% of relapses occur after the first 5 years of follow-up in this type of breast cancer.” Although ABCSG-16 found that 2 years of anastrozole was as good as 5, Gnant said that earlier studies had established that less than 2 years of AI extended treatment would not produce comparable efficacy.

“We can now conclude that after 5 years of standard adjuvant endocrine treatment, 2 additional years with AIs are sufficient as extended therapy,” he said. “There is no benefit in escalating endocrine treatment beyond 7 years. While not providing outcome benefits, the extension of 5 additional years leads to increased side effects, including fractures, and thus should be avoided.”

Gnant M, Steger G, Greil R, et al. A prospective randomized multi-center phase-III trial of additional 2 versus additional 5 years of anastrozole after initial 5 years of adjuvant endocrine therapy — results from 3,484 postmenopausal women in the ABCSG-16 trial. Presented at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX. Abstract GS3-01.