Annals of oncology : official journal of the European Society for Medical Oncology 2024 Oct 21
A phase III trial of adjuvant ribociclib plus endocrine therapy vs endocrine therapy alone in patients with HR+/HER2- early breast cancer: final invasive disease-free survival results from the NATALEE trial.
Abstract
Background
NATALEE assessed efficacy and tolerability of 3 years of adjuvant ribociclib plus NSAI compared with a nonsteroidal aromatase inhibitor (NSAI) alone in a broad population of patients with HR+/HER2- early breast cancer, including a select group without nodal involvement. This is the final preplanned analysis of invasive disease-free survival (iDFS).
Patients and methods
Premenopausal/postmenopausal women and men were randomized 1:1 to ribociclib (n=2549; 400 mg/day, 3 weeks on/1 week off for 36 months) plus NSAI (letrozole 2.5 mg/day or anastrozole 1 mg/day for 60 months) or NSAI alone (n=2552). Men and premenopausal women also received goserelin (3.6 mg once every 28 days). Patients had anatomical stage IIA (N0 with additional risk factors or N1), IIB, or III disease. The primary endpoint was iDFS. Secondary efficacy endpoints were recurrence-free survival (RFS), distant DFS (DDFS), and overall survival (OS). This final iDFS analysis was planned after ≈500 events.
Results
At data cutoff (21 July 2023), ribociclib was stopped for 1996 patients (78.3%); 1091 (42.8%) completed 3 years of ribociclib, and ribociclib treatment was ongoing for 528 (20.7%). Median follow-up for iDFS was 33.3 months. Overall, 226 and 283 iDFS events occurred with ribociclib plus NSAI vs NSAI alone, respectively. Ribociclib plus NSAI demonstrated significant iDFS benefit over NSAI alone (Hazard Ratio 0.749, 95% Confidence Interval [CI] 0.628-0.892; P=0.0012). The 3-year iDFS rates were 90.7% (95% CI 89.3%-91.8%) vs 87.6% (95% CI 86.1%-88.9%). A consistent benefit was observed across prespecified subgroups, including stage (II/III) and nodal status (+/-). DDFS and RFS favored ribociclib plus NSAI. OS data were immature. No new safety signals were observed.
Conclusions
With longer follow-up and most patients off ribociclib, NATALEE continues to demonstrate iDFS benefit with ribociclib plus NSAI over NSAI alone in the overall population and across key subgroups. Observed adverse events remained stable.
Related Questions
In which scenarios would you consider adjuvant CDK4/6 inhibitor use if there is only one ipsilateral axillary lymph node positive for microscopic disease?
For patients with stage II hormone receptor-positive, HER2-negative breast cancer that is grade 3, I would offer adjuvant ribociclib irrespective of whether they are node-positive or node-negative because such patients would be included in the NATALEE trial, and both groups had statistically signifi...
Are you routinely recommending adjuvant ribociclib now for node-negative HR+/HER2- breast cancer given data from the NATALEE trial?
Yes, I offer eligible node-negative patients, as defined by the NATALEE trial criteria, with anatomic stage II or III hormone receptor-positive breast cancer node-negative patients who are at high risk of recurrence, as defined by and would have met criteria for the NATALEE trial.The NATALEE trial d...
Would you consider adding adjuvant ribociclib for a patient who has already received 2 years of endocrine therapy and is eligible for ribociclib according to the NATALEE trial?
Since the NATALEE trial excluded patients who received more than 12 months of neoadjuvant or adjuvant endocrine therapy, I would probably not consider ribociclib for your patient, as she is too far out from initiation of endocrine therapy.
What are your top takeaways in Breast Cancer from ESMO 2024?
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