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NATALEE: three years of ribociclib after surgery in a broad population of hormone-receptor-positive early breast cancer

Three years of the CDK4/6 inhibitor ribociclib added to hormone therapy reduced relapses in stage II-III hormone-receptor-positive breast cancer, including some node-negative patients.

Open-label phase 3 trial of 5,101 patients with hormone-receptor-positive, HER2-negative stage II or III early breast cancer, including node-negative patients with high-risk features, randomised to a non-steroidal aromatase inhibitor with or without three years of ribociclib at a reduced dose (400 mg daily). Primary endpoint was invasive disease-free survival.

Three-year iDFS was 90.4% vs 87.1% (HR 0.75). Together with monarchE it established adjuvant CDK4/6 inhibition, but in a broader, lower-risk population and with a longer, lower-dose schedule.

Randomised controlled trialChanged practice5,101 participants
Authors
Slamon D, Lipatov O, Nowecki Z, et al.
What it found
  • Three-year invasive disease-free survival 90.4% vs 87.1%; HR 0.75 (95% CI 0.62-0.91).
  • Benefit was consistent across stage II and III and in node-negative and node-positive subgroups.
  • Distant disease-free survival HR 0.74.
  • Grade 3 or higher neutropenia in roughly 44% and liver enzyme elevation in roughly 8% of ribociclib patients; about one in five discontinued for adverse events.
  • Overall survival immature at the primary analysis.
What it means

Ribociclib is a second adjuvant CDK4/6 option, and the only one with data in node-negative stage II disease. Roughly 3 in 100 patients avoid a relapse or death at three years, so the decision depends heavily on individual risk, tolerance of a three-year oral drug, and cost. Whether the benefit persists after treatment ends, as it did with abemaciclib, needs longer follow-up.

Be careful
  • Absolute benefit at three years is about 3 percentage points and the trial included many patients whose baseline risk was modest.
  • Follow-up beyond the three years of treatment is limited, so durability is not yet established.
  • Open-label; a large proportion of patients stopped ribociclib early.
  • Cost of three years of therapy is substantial; cost-effectiveness has been questioned in several health systems.

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