As reported in the Journal of Clinical Oncology by Ian E. Smith, MD, of The Royal Marsden Hospital and Institute of Cancer Research, and colleagues, final results of the phase III FACE trial showed no difference in disease-free or overall survival for adjuvant letrozole vs anastrozole in postmenopausal women with hormone receptor–positive node-positive early breast cancer.¹

Study Details

In this open-label trial, 4,136 women from 271 international sites with stage IIA to IIIC invasive cancer who were within 12 weeks of breast surgery or completion of adjuvant chemotherapy were randomized between December 2005 and March 2008 to receive adjuvant letrozole at 2.5 mg (n = 2,061) or anastrozole at 1 mg (n = 2,075) once per day for 5 years or until disease recurrence. Randomization was stratified by the number of involved lymph nodes and HER2 status. The primary endpoint was 5-year disease-free survival in the intent-to-treat population.

For the letrozole vs anastrozole groups: median age was 62 years in both (40% ≥ 65 years in both); 86% vs 87% were white; World Health Organization (WHO) performance status was 0 or 1 in 99% in both; 98% vs 99% were estrogen receptor–positive, 80% vs 79% were progesterone receptor–positive, and 11% and 12% were HER2-positive; the number of involved lymph nodes was 1 to 3 in 72% vs 71% and ≥ 4 in 28% and 29%; tumor stage was T0 or T1 in 47% and 46% and T2 in 44% vs 45%; and prior therapy consisted of radiotherapy in 32% vs 30% and adjuvant chemotherapy in 63% vs 61%.

No Differences in Outcomes

Median duration of follow-up was 65 months. The 5-year estimated disease-free survival rate was 84.9% in the letrozole group vs 82.9% in the anastrozole group (hazard ratio [HR] = 0.93, P = .3150). Median disease-free survival was not reached in either group. Exploratory analysis showed similar 5-year disease-free survival rates with letrozole vs anastrozole in all evaluated subgroups, including among those with HER2-positive (86.5% vs 78.9%, HR = 0.69 , 95% confidence interval [CI] = 0.45–1.06) and HER2-negative disease (84.7% vs 83.4%, HR = 0.96, 95% CI = 0.82–1.13) and patients with 1 to 3 positive nodes (88.7% vs 87.8%, HR = 1.00, 95% CI = 0.82–1.23) and ≥ 4 positive nodes (75.1% vs 70.9%, HR = 0.86, 95% CI = 0.69–1.06), as well as among subgroups according to body mass index, tumor stage, receipt of adjuvant chemotherapy, and study region.

Letrozole did not demonstrate significantly superior efficacy or safety compared with anastrozole in postmenopausal patients with hormone receptor–positive, node-positive [early breast cancer].

— Ian E. Smith, MD, and colleagues

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The 5-year estimated overall survival rate was 89.9% vs 89.2% (HR = 0.98, P = .7916). Median overall survival was not reached in either group; at final analysis, death had occurred in 11.4% vs 11.7% of patients. Median time to distant metastases was not reached in either group; distant metastases occurred in 10.8% of patients in both groups (hazard ratio for the time to distant metastases = 0.99, P = .9391). No difference in distant disease–free survival was observed (event rate = 15.7% vs 16.2%, HR = 0.96, P = .6204). Distant recurrence was observed in 11% of both groups, with similar sites of metastasis in both. Secondary malignancies occurred in 4.1% vs 4.8% of patients.

Adverse Events

The most common adverse events of any grade in the letrozole vs anastrozole groups were arthralgia (48% vs 48%), hot flushes (33% vs 32%), fatigue (17% vs 17%), osteoporosis (11% vs 11%), myalgia (11% vs 10%), and back pain (10% vs 9%). The most common grade 3 or 4 adverse events were arthralgia (3.9% vs 3.3%), hypertension (1.2% vs 1.0%), hot flushes (0.8% vs 0.4%), myalgia (0.8% vs 0.7%), dyspnea (0.8% vs 0.5%), and depression (0.8% vs 0.6%).

Adverse events led to discontinuation of treatment in 15.1% vs 14.3% of patients and dose interruption or reduction in 8.2% vs 7.7%. Serious adverse events considered related to treatment occurred in 2.6% vs 2.3%. Death occurred in 2.0% vs 2.2% of patients; causes other than disease progression included cardiac failure (six vs two patients), pulmonary embolism (two vs four patients), and chronic obstructive pulmonary disease (one vs four patients).

The investigators concluded: “Letrozole did not demonstrate significantly superior efficacy or safety compared with anastrozole in postmenopausal patients with hormone receptor–positive, node-positive [early breast cancer].” ■

Disclosure: The study was supported by Novartis Pharmaceuticals. For full disclosures of the study authors, visit www.jco.ascopubs.org.

Reference

1. Smith I, Yardley D, Burris H, et al: Comparative efficacy and safety of adjuvant letrozole versus anastrozole in postmenopausal patients with hormone receptor-positive, node-positive early breast cancer: Final results of the randomized phase III Femara versus Anastrozole Clinical Evaluation (FACE) trial. J Clin Oncol 35:1041-1048, 2017.