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Timing and Patterns of Relapse-Related Events Following Adjuvant CDK4/6 Inhibitors Combined With Endocrine Therapy in
Huihui Chen1,2, Shijie Wu1,2, Yangyang Shan3
1Department of Breast Surgery and Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Background:
Adjuvant CDK4/6 inhibitors improve outcomes in hormone receptor-positive, HER2-negative (HR+/HER2-) early breast cancer, yet some patients still experience recurrence. Early relapse in particular is associated with poor prognosis, but the timing and patterns of recurrence following this treatment remain undefined, limiting further therapeutic strategy development.
Materials And Methods:
We analyzed pivotal trials of adjuvant CDK4/6 inhibitors in early-stage HR+/HER2- breast cancer to assess the temporal distribution of iDFS events. Invasive disease-free survival (iDFS) and overall survival (OS) data were extracted from Kaplan-Meier curves using PlotDigitizer. Events were evaluated up to 60 months, a time frame with consistent follow-up across trials. The primary endpoint was the proportion of early versus total iDFS events and deaths by 60 months. The types and patterns of first iDFS event, as well as adverse events, were also discussed.
Results:
The 5-year iDFS in CDK4/6 inhibitor-containing arms were as follows: 85.5% (NATALEE), 83.1% (monarchE), 84.2% (PALLAS), 67.9% (PENELOPE-B). Early relapse-related events (≤ 36 months) accounted for 63.5%, 63.9%, 62.7%, and 60.8% of total iDFS events, respectively, all proportions broadly similar to those observed in the control arms. The temporal distribution of iDFS event rates within consecutive 6-month intervals appeared generally consistent. Distant metastasis constituted the predominant form of the first iDFS event, with bone as the most common metastatic site. The most frequently reported adverse events included neutropenia and diarrhea. Diarrhea was more prevalent with abemaciclib, whereas neutropenia occurred more frequently with palbociclib.
Conclusion:
Adjuvant CDK4/6 inhibitors (ribociclib and abemaciclib) demonstrated iDFS benefits in monarchE and NATALEE. In our exploratory analysis, the temporal distribution of iDFS events appeared broadly consistent across trials, with no obvious concentration in any specific period. Given that early iDFS events (≤ 36 months) accounted for a substantial proportion of all events, further prospective studies are needed to optimize treatment for this high-risk population.
