Adjuvant ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+/HER2− early breast cancer (EBC): NATALEE 6-y overall survival (OS) and efficacy outcomes

doi:10.1016/j.annonc.2026.10.1288

NATALEE

Paziente / Popolazione Intervento / Esposizione Confronto Esito

In patients with high-risk stage II/III HR+/HER2− early breast cancer, adjuvant ribociclib plus a nonsteroidal aromatase inhibitor improved overall survival and invasive disease-free survival at 6 years compared with a nonsteroidal aromatase inhibitor alone.

N

—pazienti

Disegno

Phase 3 trial randomising patients 1:1 with HR+/HER2- stage II/III early breast cancer (stage IIA if N1 or N0 with additional high-risk factors, stage IIB or stage III) to adjuvant ribociclib for 3 years plus a nonsteroidal aromatase inhibitor for 5 years or a nonsteroidal aromatase inhibitor alone, with goserelin for premenopausal women and men (NCT03701334).

Esito

Overall survival, the focus of this prespecified analysis at 6 years of follow-up. The abstract does not name the trial's primary endpoint, but it reports that the trial had already shown a statistically significant invasive disease-free survival benefit. Other endpoints were breast cancer-specific survival, invasive disease-free survival, distant disease-free survival and distant recurrence-free survival.

RisultatoWith a median OS follow-up of 66.5 months, overall survival favoured ribociclib + NSAI over NSAI alone (HR 0.809, 95% CI 0.661-0.989; nominal 1-sided P = .019). The absolute benefit was 1.2% at 5 years (93.89% vs 92.73%) and 2.1% at 6 years (91.86% vs 89.73%). Breast cancer-specific survival HR 0.706 (95% CI 0.559-0.890). With a median iDFS follow-up of 66.3 months, iDFS HR 0.741 (95% CI 0.646-0.849; nominal 1-sided P < .0001). The absolute iDFS benefit was 4.1% at 5 years (85.32% vs 81.24%) and 5.3% at 6 years (83.23% vs 77.92%). DDFS HR 0.744 (95% CI 0.646-0.858) and DRFS HR 0.738 (95% CI 0.634-0.858). No new safety signals were observed.

Slamon D, Hortobagyi G, Stroyakovskiy D, et al. Annals of Oncology. 2026. 10.1016/j.annonc.2026.10.1288

Discussione e critica

At 6 years, with all patients off ribociclib for a median of 38 months, the invasive disease-free survival benefit holds up and overall survival now favours the combination, with breast cancer-specific survival pointing the same way. The OS P value is nominal and 1-sided, so the abstract does not present it as formal proof against a prespecified significance boundary, and the absolute OS gain is 2.1% at 6 years. The abstract does not give the number randomised, the number of deaths, blinding, subsequent treatments or subgroup estimates, and its safety summary is limited to no new signals. Whether the absolute OS difference keeps widening will need longer follow-up.