NATALEE update: Ribociclib + NSAI well tolerated

Latest findings from the ongoing phase III NATALEE trial have shown that 3-year treatment with adjuvant ribociclib, in combination with a nonsteroidal aromatase inhibitor (NSAI), remained well tolerated in patients with HR+/HER2- early-stage breast cancer (EBC).

At the time of the analysis, 98 percent of patients treated with the combination regimen and 87.8 percent of those treated with an NSAI alone experienced adverse events (AEs). No new safety signals were observed with ribociclib + NSAI, consistent with previous findings.

“Neutropenia, infections, and arthralgia were the most common adverse events [AEs] related to the experimental arm,” reported lead study author Dr Carlos Barrios, director at the Oncology Research Center at Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul, Brazil, at ESMO Breast 2024. “Most grade 3 AEs were asymptomatic laboratory findings that were easily identifiable, manageable, and reversible.”

He noted that dose reductions with ribociclib due to AEs did not affect its efficacy. At the 25th percentile (1.87 months) following randomization, 13 of 123 patients who required dose reductions experienced iDFS* events vs 208 of 2,315 patients who did not require dose reductions.

At the 50th percentile (3.17 months), 19 of 276 patients who required dose reductions had iDFS events vs 193 of 2,117 patients who did not. At the 75th percentile (7.28 months), 35 of 406 patients requiring reductions and 158 of 1,933 patients not requiring dose reductions experienced iDFS events.

Adjuvant therapy for HR+/HER2- EBC

In NATALEE, patients received ribociclib 400 mg/day (using a 3-weeks on, 1-week off schedule) + NSAI (letrozole 2.5/day or anastrozole 1 mg/day based on investigator’s discretion) or an NSAI alone. Men and premenopausal women also received a luteinizing hormone-releasing hormone agonist (goserelin).

Updated results showed that 79.1 percent of patients in the safety set had discontinued ribociclib. About 69.4 percent had completed 2 years of ribociclib, whereas 43.2 percent had completed 3 years of ribociclib. [ESMO Breast 2024, abstract 113MO]

“Importantly, 20.9 percent of patients were still on ribociclib up to this point,” Barrios pointed out. “With most patients completing treatment, we can confirm that ribociclib-related AEs occurred early in the treatment, allowing for prompt dose adjustments of ribociclib.”

Better iDFS with combo regimen

Results from a prespecified interim analysis of NATALEE published in March showed that adding adjuvant ribociclib to an NSAI significantly improved iDFS rates compared with NSAI alone in patients with HR+/HER2- EBC. [N Engl J Med 2024;390:1080-1091]

“The benefit of this combined regimen has been consistent across different subgroups, including patients with stage II and III disease and those with both node-negative and node-positive disease,” Barrios shared during his presentation.

At a median follow-up of 27.7 months (data cutoff January 11, 2023), the iDFS rate was 90.4 percent with the combination regimen vs 87.1 percent with NSAI alone (hazard ratio, 0.75; p=0.003), for a difference of 3.3 percentage points. Distant disease-free and recurrence-free survival rates also favoured ribociclib + NSAI.