BREAST CANCER · MEDICAL · ADVANCED / METASTATIC
BOLERO-2
Clinical question: In HR-positive/HER2-negative advanced breast cancer progressing after a nonsteroidal aromatase inhibitor, does everolimus plus exemestane improve progression-free survival?
Trial design and population
724 postmenopausal women with HR-positive/HER2-negative advanced breast cancer refractory to letrozole or anastrozole.
Intervention: everolimus 10 mg orally daily plus exemestane 25 mg daily vs placebo plus exemestane.
Primary endpoint: progression-free survival.
Key results and outcome visualization
Final investigator-assessed median PFS was 7.8 vs 3.2 months (HR 0.45, 95% CI 0.38–0.54). Median OS was 31.0 vs 26.6 months (HR 0.89, 95% CI 0.73–1.10; not statistically significant).
Median progression-free survival · final analysis
Median PFS difference 4.6 months is not an NNT. No statistically significant OS benefit was demonstrated.
Absolute Effect
NNT: Not calculated; median PFS difference is not a valid NNT.
NNH: Not quantifiable from a single selected fixed-time excess-harm endpoint.
Safety and treatment burden
Clinically important grade 3+ toxicities include stomatitis, infections, hyperglycaemia, fatigue and noninfectious pneumonitis. Stomatitis prophylaxis and metabolic monitoring are important; dose modifications and discontinuation are common.
Follow-up and limitations
Final OS analysis after long follow-up. This trial predates routine CDK4/6 inhibitors and newer molecularly selected agents. Current sequencing depends on prior therapy and tumour genomics.
Clinical interpretation
Current-practice context · reviewed 20 October 2026
Historical evidence is separated from current sequencing. Confirm current guidelines, local regulatory status, biomarkers, prior therapies and patient-specific contraindications before applying these results.