Insight

Mar 22, 2024, 23:32

Piotr J. Wysocki: Ribociclib combined with an aromatase inhibitor in the adjuvant treatment of breast cancer – interim analysis of Natalee study

Piotr J. Wysocki, Head of the Oncology Department at the

“The Natalee phase III study compared adjuvant therapy of early breast cancer (BC) based on ribociclib and nonsteroidal aromatase inhibitor (AI) combination with standard endocrine therapy based on AI has just been published in NEJM. The study randomized 5101 patients in a 1:1 ratio to investigational arm – ribociclib (400 mg daily for 21 days with 7 days off) for 36 months plus AI (letrozole or anastrozole) for 60 months or control arm AI for 60 months. The study enrolled patients with (i) stage III or IIB disease irrespectively of nodal status, (ii) patients with stage IIA disease if they had at least one lymph node involved, or (iii) patients without involvement if they had grade 2 tumor with a Ki-67 ≥20% or had a high genomic risk.
After a median follow-up of 27 months, the risk of invasive disease, recurrence, or death was significantly lower (by 25.2%) in the investigational arm than in the control arm (HR=0.75; 95%CI 0.62 to 0.91). At 3 years, recurrence-free survival was 91.7% with ribociclib plus an AI and 88.6% with an NSAI alone (HR for recurrence or death – 0.72; 95% CI, 0.58 to 0.88). The rate of death at 3 years was 2.4% in the ribociclib–AI group and 2.9% in the AI group, which translated into a nonsignificant difference in the risk of death – HR=0.76 (95% CI, 0.54 to 1.07)
18.9% of patients required early discontinuation of ribociclib. The most common adverse events of any grade that led to discontinuation of any trial treatment were liver-related events and arthralgia (8.9% vs. 0.1% and 1.3% vs. 1.9% in the experimental and control arms, respectively).
Ribociclib, like abemaciclib, has significantly decreased the risk of recurrence in high-risk patients at the cost of significantly increased toxicity. This drug will soon join abemaciclib as the recommended adjuvant treatment option in patients with HR+/HER2- breast cancer. However, one has to recognize that the long-term efficacy results, which can prove the curability potential of CDK4/6i+IA combinations in adjuvant treatment, still need to be elucidated since overall survival data is highly immature. We need confirmation of overall survival improvement and robust quality-of-life data to dispel doubts about the true benefit of intensified adjuvant treatment, especially in lower-risk patients.
DOI: 10.1056/NEJMoa2305488”

Source: Piotr J. Wysocki/LinkedIn