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Background <p>The phase 3 NATALEE trial demonstrated sustained invasive disease–free survival benefit for patients with stage II or III HR+/HER2−  early breast cancer (EBC) treated with ribociclib + nonsteroidal aromatase inhibitor (NSAI) vs. NSAI alone. Here we report detailed safety and tolerability data from NATALEE to further inform clinical decision-making.</p> Methods <p>In NATALEE, men and pre- and postmenopausal women with HR+/HER2−  EBC were randomized 1:1 to ribociclib 400&#xa0;mg/day (3 weeks on/1 week off; 36 months) + NSAI (anastrozole or letrozole; ≥60 months) or NSAI alone. Men and premenopausal women also received goserelin. Safety analyses included incidence of treatment-emergent adverse events (AEs) as well as severity, timing, management, and outcomes. Safety parameters among older vs. younger patients were also assessed.</p> Results <p>At this 45.7-month median follow-up (data cutoff: April 29, 2024), the safety analysis set comprised 4967 patients receiving ribociclib + NSAI (<i>n</i> = 2526) or NSAI alone (<i>n</i> = 2441). The most common grade ≥ 3 AEs occurring with ribociclib + NSAI vs. NSAI alone, respectively, were neutropenia (grouped term; 44.4% vs. 0.9%), liver-related AEs (grouped term; 8.6% vs. 1.7%), and leukopenia (grouped term; 8.0% vs. 0.4%). Drug-related serious AEs occurred in 2.8% vs. 0.5%, respectively. Among patients receiving ribociclib + NSAI, AE-related ribociclib discontinuation occurred in 20.2% (median onset, 4.3 months), with 9.0% of instances occurring because of liver-related AEs. AE-related ribociclib dose interruptions (66.8%; median onset, 1.8 months) and dose reductions (23.0%; median onset, 3.2 months) were primarily driven by neutropenia (dose interruptions, 43.4%; dose reductions, 14.1%). In the ribociclib + NSAI arm, AE incidence and ribociclib dose interruptions or reductions occurred at similar rates among older patients (≥ 65 years) and younger patients (&lt; 65 years). A higher proportion of older patients permanently discontinued ribociclib due to AEs (28.1%; <i>n</i> = 113/402) vs. younger patients (18.6%; <i>n</i> = 396/2124), most commonly due to alanine aminotransferase increased (older, 8.5%; younger, 7.0%).</p> Conclusions <p>Overall, ribociclib 400&#xa0;mg was well tolerated, including in older patients, and AEs were manageable with current NATALEE label recommendations of dose interruptions and reductions.</p> <p><i>Trial registration</i> ClinicalTrials.gov identifier: NCT03701334 (registered September 21, 2018).</p>

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Safety and treatment duration of ribociclib + nonsteroidal aromatase inhibitor in HR+/HER2− early breast cancer: a phase 3 randomized controlled trial (NATALEE)

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  • 发表日期：

    2026年8月4日

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  • H. S. Rugo,
  • N. Harbeck,
  • G. N. Hortobagyi,
  • J. O’Shaughnessy,
  • C.-S. Huang,
  • M. Martin,
  • D. Juric,
  • B. Pistilli,
  • B. Xu,
  • M. De Laurentiis,
  • M. Untch,
  • K. Afenjar,
  • M. Gao,
  • Z. Li,
  • N. Bolotova,
  • S. Waters,
  • C. Barrios

摘要

Background

The phase 3 NATALEE trial demonstrated sustained invasive disease–free survival benefit for patients with stage II or III HR+/HER2−  early breast cancer (EBC) treated with ribociclib + nonsteroidal aromatase inhibitor (NSAI) vs. NSAI alone. Here we report detailed safety and tolerability data from NATALEE to further inform clinical decision-making.

Methods

In NATALEE, men and pre- and postmenopausal women with HR+/HER2−  EBC were randomized 1:1 to ribociclib 400 mg/day (3 weeks on/1 week off; 36 months) + NSAI (anastrozole or letrozole; ≥60 months) or NSAI alone. Men and premenopausal women also received goserelin. Safety analyses included incidence of treatment-emergent adverse events (AEs) as well as severity, timing, management, and outcomes. Safety parameters among older vs. younger patients were also assessed.

Results

At this 45.7-month median follow-up (data cutoff: April 29, 2024), the safety analysis set comprised 4967 patients receiving ribociclib + NSAI (n = 2526) or NSAI alone (n = 2441). The most common grade ≥ 3 AEs occurring with ribociclib + NSAI vs. NSAI alone, respectively, were neutropenia (grouped term; 44.4% vs. 0.9%), liver-related AEs (grouped term; 8.6% vs. 1.7%), and leukopenia (grouped term; 8.0% vs. 0.4%). Drug-related serious AEs occurred in 2.8% vs. 0.5%, respectively. Among patients receiving ribociclib + NSAI, AE-related ribociclib discontinuation occurred in 20.2% (median onset, 4.3 months), with 9.0% of instances occurring because of liver-related AEs. AE-related ribociclib dose interruptions (66.8%; median onset, 1.8 months) and dose reductions (23.0%; median onset, 3.2 months) were primarily driven by neutropenia (dose interruptions, 43.4%; dose reductions, 14.1%). In the ribociclib + NSAI arm, AE incidence and ribociclib dose interruptions or reductions occurred at similar rates among older patients (≥ 65 years) and younger patients (< 65 years). A higher proportion of older patients permanently discontinued ribociclib due to AEs (28.1%; n = 113/402) vs. younger patients (18.6%; n = 396/2124), most commonly due to alanine aminotransferase increased (older, 8.5%; younger, 7.0%).

Conclusions

Overall, ribociclib 400 mg was well tolerated, including in older patients, and AEs were manageable with current NATALEE label recommendations of dose interruptions and reductions.

Trial registration ClinicalTrials.gov identifier: NCT03701334 (registered September 21, 2018).