Treatment to 10 years and beyond beneficial for some patients
Extending adjuvant endocrine therapy with an aromatase inhibitor to 10 years led to significant improvement in disease-free survival (DFS) and distant (DDFS) in postmenopausal women with hormone receptor-positive (HR-positive) breast cancer, Japanese investigators reported here.
Patients randomized to receive an additional 5 years of endocrine therapy had a DFS of 91.9% at 5 years post-randomization as compared with 84.4% among patients who stopped endocrine treatment after 5 years. However, the improved DFS did not translate into an improvement in overall survival (OS).
On the basis of the trial results, “I would recommend that patients with node-positive disease continue an aromatase inhibitor for 10 years,” said Shoichiro Ohtani, MD, PhD, of Hiroshima Citizens Hospital, at the San Antonio Breast Cancer Symposium (SABCS).
In a separate SABCS study, investigators in the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) performed a meta-analysis of 11 randomized trials of extended AI treatment after prior endocrine therapy. The results showed that the benefits of extended therapy differed according to type or prior therapy, with a larger reduction in the risk of recurrence when the AI was preceded by tamoxifen.
Upfront AI therapy for 2 to 3 years after tamoxifen is a standard approach to treatment for postmenopausal HR-positive breast cancer. Extended endocrine therapy can reduce the risk of late recurrence, said Ohtani. Data from several recent trials showed that extended AI therapy reduced the risk of secondary breast cancer, but had only a modest impact on DDFS.
Previous studies evaluating extended AI therapy involved various drugs in the category. Ohtani reported findings from the randomized AERAS trial, which specifically evaluated anastrozole (Arimidex) for extended treatment. The trial involved postmenopausal women with primary HR-positive breast cancer treated with anastrozole or tamoxifen plus anastrozole for ≥2 years, for a total of 5 years.
Patients who had completed 5 years of endocrine therapy were randomized to no additional therapy or to an additional 5 years of anastrozole. Ohtani reported findings from a median follow-up of 4.9 years for the extended-treatment phase. The primary endpoint was DFS, and secondary endpoints included DDFS, OS, and safety.
Data analysis included 1,683 patients who had a median age of 64 and BMI 23. About 95% of the patients had stage T1 or T2 disease, and about 80% had N0 nodal status ( about 98% N0-1). About 40% of the patients had received adjuvant chemotherapy, and 91% of the patients had received 5 years of anastrozole before entering the extended-treatment study. Ohtani said 75% of the patients who stopped treatment completed the trial compared with 70.1% of patients randomized to an additional 5 years of anastrozole.
The results showed a total of 117 local recurrences, including 47 local recurrences, 15 in the anastrozole arm and 32 in the patients who stopped endocrine treatment at 5 years. The additional 5 years of AI therapy was associated with a 45% reduction in the DFS hazard (P=0.0004). An extensive subgroup analysis did not identify any group of patients who did not benefit from extended endocrine therapy.
Ohtani said 70 patients developed distant metastases, 23 in the extended-AI arm and 47 in the control group. The difference represented a 49% reduction in the hazard ratio for DDFS (P=0.0077). Only seven patients died during follow-up in the extended-treatment study — four in the anastrozole arm and three in the group that did not continue therapy.
Patients allocated to anastrozole had higher rates of adverse events, including bone fractures (2.8% vs 1.1%), osteoporosis (33% vs 28%), arthralgia (19.2% vs 11.7%), joint stiffness (11.7% vs 4.9%), and hot flashes (6.7% vs 3.1%). Grade ≥3 adverse events were uncommon (<1% for each of the predefined adverse events of interest).
The EBCTCG meta-analysis involved a total of 22,192: 7,500 treated for 5 years with tamoxifen; 12,300 treated for 5 to 10 years with tamoxifen followed by an AI; and 4,800 who received only an AI for 5 years. Median follow-up in the trial ranged between 4.9 and 6.5 years, said Richard Gray, of the University of Oxford in England.
The overall analysis showed that extended endocrine therapy with an AI led to a 24% reduction in the risk of any recurrence (9.5% vs 7.0%, 95% CI 0.70-0.83, P<0.00001); a 15% reduction in the risk of distant recurrence (6.1% vs 5.1%, 95% CI 0.77-0.95, P=0.004); and a nonsignificant reduction in breast cancer mortality (3.1% vs 2.8%, P=0.09).
Trials that evaluated anastrozole after 5 years of tamoxifen showed a significant reduction in any recurrence (10.7% vs 7.1%, relative risk 0.67, 95% CI 0.57-0.77, P<0.00001); distant recurrence (6.7% vs 5.2%, RR 0.77, 95% CI 0.63-0.93, P=0.008); and breast cancer mortality (3.5% vs 2.7%, RR 0.77, 95% CI 0.59-1.00, P=0.05).
The trials of extended AI treatment after 5-10 years of tamoxifen-AI therapy collectively showed a reduction in any recurrence (9.2% vs 7.1%, RR 0.82, 95% CI 0.73-0.93, P=0.002), but not distant recurrence (6.2% vs 5.3%) or breast cancer mortality (3.1% vs 2.9%).
The trials of extended AI treatment after 5 years of initial AI treatment also showed a reduction in the risk of any recurrence (7.9% vs 6.6%, RR 0.76, 95% CI 0.61-0.95, P=0.02, but not distant recurrence (4.7% vs 4.4%) or breast cancer mortality (2.7% vs 2.4%).
Gray said that the impact of extended AI therapy on recurrence risk depends on the type of prior endocrine therapy. Among women with prior tamoxifen treatment, extended AI therapy resulted in a larger risk reduction (RR 0.67, 95% CI 0.57-0.79, P<0.00001) as compared with women who received an AI for at least part of their initial endocrine therapy (RR 0.81, 95% CI 0.73-0.90, P=0.00010).