Messaggi chiave
- NATALEE è uno studio internazionale di fase 3, randomizzato, in aperto, che ha valutato efficacia e sicurezza di ribociclib adiuvante in associazione a endocrinoterapia (ET) rispetto a ET da sola in 5101 pazienti con carcinoma mammario precoce (stadio II-III) HR+/HER2-. L’endpoint primario era la sopravvivenza libera da malattia invasiva (IDFS).
- A un follow-up di 3 anni, ribociclib + ET ha prodotto un miglioramento significativo dei tassi di IDFS rispetto al trattamento di controllo (90,4 vs 87,1%), con una riduzione del rischio di malattia invasiva, recidiva o morte del 25% (p = 0,003). Anche gli endpoint secondari di sopravvivenza libera da malattia a distanza e sopravvivenza libera da recidiva hanno favorito il braccio sperimentale.
- Non sono emersi nuovi segnali di sicurezza. La percentuale di pazienti con ≥1 evento avverso (EA) è risultata pari al 97,9 vs 87,1% con ribociclib + ET rispetto a ET da sola e gli EA più comuni di qualsiasi grado sono stati neutropenia, artralgia ed eventi di tossicità epatica. Sarà necessario un ulteriore follow-up per valutare gli esiti di efficacia a lungo termine.
Abstract
Background
- Ribociclib has been shown to have a significant overall survival benefit in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer.
- Whether this benefit in advanced breast cancer extends to early breast cancer is unclear.
Methods
- In this international, open-label, randomized, phase 3 trial, we randomly assigned patients with HR-positive, HER2-negative early breast cancer in a 1:1 ratio to receive ribociclib (at a dose of 400 mg per day for 3 weeks, followed by 1 week off, for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI; letrozole at a dose of 2.5 mg per day or anastrozole at a dose of 1 mg per day for ≥5 years) or an NSAI alone.
- Premenopausal women and men also received goserelin every 28 days.
- Eligible patients had anatomical stage II or III breast cancer. Here we report the results of a prespecified interim analysis of invasive disease-free survival, the primary end point; other efficacy and safety results are also reported. Invasive disease-free survival was evaluated with the use of the Kaplan-Meier method.
- The statistical comparison was made with the use of a stratified log-rank test, with a protocol-specified stopping boundary of a one-sided P-value threshold of 0.0128 for superior efficacy.
Results
- As of the data-cutoff date for this prespecified interim analysis (January 11, 2023), a total of 426 patients had had invasive disease, recurrence, or death.
- A significant invasive disease-free survival benefit was seen with ribociclib plus an NSAI as compared with an NSAI alone.
- At 3 years, invasive disease-free survival was 90.4% with ribociclib plus an NSAI and 87.1% with an NSAI alone (hazard ratio for invasive disease, recurrence, or death, 0.75; 95% confidence interval, 0.62 to 0.91; P = 0.003).
- Secondary end points – distant disease-free survival and recurrence-free survival – also favored ribociclib plus an NSAI.
- The 3-year regimen of ribociclib at a 400-mg starting dose plus an NSAI was not associated with any new safety signals.
Conclusions
- Ribociclib plus an NSAI significantly improved invasive disease-free survival among patients with HR-positive, HER2-negative stage II or III early breast cancer.
Note: Funded by Novartis; NATALEE ClinicalTrials.gov number, NCT03701334