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Research Article
29 August 2025

Matching-adjusted indirect comparison of ribociclib + nonsteroidal aromatase inhibitor versus abemaciclib + endocrine therapy in hormone receptor-positive/HER2-negative early breast cancer

Authors: Stephen Chia https://orcid.org/0000-0001-7070-4386 [email protected], Jie Li, Fei Ma, Daniel Stellato, Andriy Danyliv, Ilia Ferrusi, Huilin Hu, Murat Akdere, and Andreas MakrisAuthor Info & Affiliations
Volume 14, Number 10
https://doi.org/10.57264/cer-2025-0082
PDFFormats

Abstract

Aim: Ribociclib + nonsteroidal aromatase inhibitor (NSAI) and abemaciclib + endocrine therapy (ET) are approved for high-risk hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer based on data from the NATALEE and monarchE trials, respectively. No trials have directly compared efficacy and safety of adjuvant ribociclib and abemaciclib. This study compared relative efficacy and safety of adjuvant ribociclib + NSAI versus abemaciclib + ET using matching-adjusted indirect comparison (MAIC). Materials & methods: Individual patient data from NATALEE and aggregate data from monarchE were analyzed, with patients from NATALEE selected to match the key eligibility criteria of monarchE cohort 1. Unanchored MAIC was used to compare invasive disease-free survival, distant relapse–free survival, and grade ≥3 treatment-emergent adverse events between treatment arms in NATALEE versus monarchE. Cox regression was used to estimate hazard ratios pre- and post-MAIC weighting. Logistic regression was used to estimate odds ratios (ORs). Results: After weighting, the effective sample size for the ribociclib + NSAI arm of NATALEE was 448. Cox regression yielded similar invasive disease-free survival with weighted ribociclib + NSAI versus abemaciclib + ET (hazard ratio, 0.901; 95% CI: 0.678–1.197). Unweighted efficacy comparisons were consistent with the weighted approach. Lower odds (OR <1) for diarrhea, leukopenia and lymphopenia and higher odds (OR >1) for increased alanine aminotransferase and neutropenia with ribociclib + NSAI versus abemaciclib + ET were noted before and after weighting. Sensitivity analyses were consistent with the primary analysis. Conclusion: This MAIC suggests similar efficacy between ribociclib + NSAI and abemaciclib + ET but different safety profiles in the HR+/HER2- early breast cancer patient population corresponding to the monarchE cohort 1, which has implications for treatment decisions. This analysis has limitations inherent to unanchored MAIC and should be interpreted in context of the trials and with clinical judgement.

Plain language summary

What is this article about?

Most patients with breast cancer are diagnosed at an early stage. For patients with hormone receptor-positive/human epidermal growth factor receptor 2–negative (HR+/HER2-) early breast cancer (EBC), endocrine therapy (ET) has been the standard treatment in clinics. However, in many of these patients, there is a high risk of the cancer coming back even after ET. Phase III clinical trials NATALEE and monarchE have shown that when ribociclib and abemaciclib, respectively, are added to ET, patients with EBC are able to live cancer free longer. Thus, ribociclib and abemaciclib, with ET, have now been approved to treat patients with HR+/HER2- EBC who have a high risk of the cancer coming back. This study used data from NATALEE and monarchE to compare benefits of adding ribociclib and abemaciclib, respectively, to ET. As patients that are allowed to participate in different trials may have different clinical characteristics, these differences need to be adjusted for accurate comparisons.

What were the results?

Following adjustment for these differences, this study found that patients with HR+/HER2- EBC treated with ribociclib + ET were cancer free for a similar length of time as patients treated with abemaciclib + ET. Finally, patients on abemaciclib had higher risk of diarrhea and lower white blood cell counts and lymphocyte counts as side effects, while patients on ribociclib had higher risk of liver enzyme elevation and lower neutrophil counts.

What do the results mean?

While these data are not conclusive, they can be useful when deciding on a treatment course for patients with high-risk HR+/HER2- EBC.

Shareable abstract

Indirect treatment comparison suggests similar efficacy benefits with potential difference in safety profiles for ribociclib and abemaciclib in the treatment of HR+/HER2- early breast cancer after considering cross-trial differences. #MAIC #breastcancer #EBC

Supplementary Material

File (supplementary materials.docx)

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