Limited benefit to extending letrozole therapy in postmenopausal breast cancer patients
Five years of extended therapy with the aromatase inhibitor (AI) letrozole did not improve survival in postmenopausal breast cancer patients, according to findings of the NRG Oncology/NSABP B-42 trial presented at the San Antonio Breast Cancer Symposium (SABCS 2016) held in Texas, US.
After a median follow-up period of 6.9 years, extended letrozole therapy did not improve disease-free survival (DFS) compared with placebo (292 vs 339 events in the letrozole and placebo arms, respectively; hazard ratio [HR], 0.85, 95 percent confidence interval [CI], 0.73–0.999; p=0.048). The 7-year DFS was 84.7 percent vs 81.3 percent in the letrozole and placebo arms, respectively. [SABCS 2016, abstract S1-05]
Extended letrozole therapy also did not improve overall survival (OS; HR, 1.15, 95 percent CI, 0.99–1.44; p=0.22; 7-year OS was 91.8 percent vs 92.3 percent in the letrozole and placebo arms, respectively).
There was a reduction in the risk of recurrence or contralateral breast cancer as first event (breast cancer-free interval [BCFI] events) in women on extended letrozole compared with placebo (127 vs 179 events; HR, 0.71, 95 percent CI, 0.56–0.89; p=0.003), with a 7-year cumulative incidence of 6.7 percent in the letrozole arm vs 10 percent in the placebo arm. Incidence of distant recurrence was also reduced in women on letrozole (73 vs 102 events; HR, 0.72, 95 percent CI, 0.53–0.97; p=0.03).
Between September 2006 and January 2010, 3,966 postmenopausal women with stage I-IIIA HR-positive breast cancer previously treated with adjuvant hormonal therapy (AI for 5 years or tamoxifen for ≤3 years followed by AI to complete 5 years) were randomized to receive either letrozole (2.5 mg/day) or placebo for 5 years.
Letrozole treatment discontinuation due to adverse events occurred in 9.6 percent of participants, while discontinuation due to withdrawal/refusal and disease progression occurred in 13.8 and 4.1 percent of participants, respectively.
Incidence of osteoporotic fractures was comparable between women on letrozole and placebo (91 vs 78 events; HR, 1.19, 95 percent CI, 0.88–1.60; p=0.27), as was incidence of arterial thrombotic events (71 vs 59 events; HR, 1.21, 95 percent CI, 0.85–1.70; p=0.29).
“Letrozole did not significantly increase risk of osteoporotic fractures but risk of arterial thrombotic events was elevated for letrozole after 2.5 years,” said trial lead investigator Dr Terry Mamounas, medical director of the Comprehensive Breast Program at UF Health Cancer Center in Orlando, Florida, US.
“Our findings suggest that careful assessment of potential risks and benefits is required before recommending extended letrozole therapy in patients with early-stage breast cancer,” said Mamounas. Factors to be considered include patient and tumour characteristics, existing comorbidities, bone mineral density, and AI tolerance in the initial 5 years, he said.