Final analysis of NRG oncology/NSABP B-42, a randomized, double-blinded, placebo-controlled trial of extended letrozole in postmenopausal women with hormone-receptor positive breast cancer who have completed previous adjuvant therapy with an aromatase inhibitor

NSABP B-42

Patient / Population Intervention / Exposure Comparison Outcome

In postmenopausal women with hormone-receptor positive breast cancer who were disease-free after 5 years of aromatase inhibitor-based adjuvant therapy, 5 further years of letrozole modestly improved 15-year disease-free survival, but not overall survival, compared with placebo.

N

3,966patients

Design

Randomised 1:1, double-blinded, placebo-controlled trial (phase not stated) in 3,966 postmenopausal patients with stage I-III hormone-receptor positive breast cancer who were disease-free after 5 years of an aromatase inhibitor or up to 3 years of tamoxifen followed by an aromatase inhibitor for a total of 5 years, assigned to 5 years of letrozole or placebo, stratified by pathologic nodal status, prior tamoxifen and baseline DEXA T score (NCT00382070).

Endpoint

Disease-free survival (DFS).

Result15-year DFS 61.6% with letrozole vs 56.5% with placebo (HR 0.85, 95% CI 0.77-0.94), reported as a significant improvement. 15-year breast cancer-free interval risk 14.7% vs 18.3% (HR 0.78, 95% CI 0.67-0.92) and 15-year distant recurrence risk 6.9% vs 9.7% (HR 0.72, 95% CI 0.57-0.91). No significant improvement in overall survival: 15-year OS 74.0% vs 72.3% (HR 0.92, 95% CI 0.82-1.05). Median follow-up 15.9 years, with 538 additional DFS events since the 10-year update. The DFS effect was consistent across subgroups by stratification factors.

Mamounas EP, Bandos H, Geyer CE, et al. Presented at ESMO Congress 2026, abstract LBA24, 23 October. Not yet published.

Discussion & critique

This final analysis has mature follow-up (median 15.9 years) from a large double-blinded, placebo-controlled trial and shows that the modest DFS benefit of extended letrozole persisted, with no attenuation from year 10 to year 15. The benefit appears in DFS, breast cancer-free interval and distant recurrence, but overall survival was not significantly improved, so the gain in a hard endpoint is still unproven. The abstract reports no P values, no safety or bone-related toxicity data and no adherence or treatment completion figures, so the absolute benefit cannot be weighed against harms. Subgroup consistency is reported only for the stratification factors.