Episode 1: The NATALEE trial

The Phase III NATALEE trial assessed the impact of ribociclib (RIB) plus endocrine therapy (ET) on early breast cancer (EBC) outcomes, including a diverse group of stage II or III HR+/HER2− EBC patients. RIB was administered for 3 years at a dose of 400 mg.

Results from an interim analysis of invasive disease–free survival (iDFS) revealed that RIB + ET significantly improved iDFS compared to ET alone, with a 3-year iDFS rate of 90.4% versus 87.1%. This benefit was consistent across various subgroups. Secondary endpoints, including overall survival, recurrence-free survival, and distant disease–free survival, also favoured RIB. The safety profile of RIB at 400 mg was favourable.

During the discussion, our experts highlighted the potential impact of CDK4-6 inhibitors such as abemaciclib and ribociclib on clinical practice. They emphasized that the decision-making process would depend on regulators’ perspective, future data analysis, and evolving safety profiles. The experts also stressed the importance of continued patient follow-up as the data remains relatively immature, with a short follow-up duration and a limited percentage of patients having completed treatment. They also emphasized the need to distinguish between curative and metastatic settings and the expectation of evolving positive results, similar to the MonarchE trial with abemaciclib. Finally, Prof De Azambuja invited everyone to pay attention to the upcoming virtual ESMO presidential session in September, where quality of life data from the NATALEE trial will be presented, further enriching our understanding of the study’s impact.