monarchE: No predictive biomarkers revealed with molecular profiling

The survival benefit of abemaciclib was recently demonstrated in the phase 3 monarchE trial. According to the molecular profiling of tumour samples, this benefit is consistent across all breast cancer-intrinsic molecular subgroups, for both high and low Oncotype DX risk scores, and for all most prevalent genomic alterations with the exception of MYC amplification.

Patients with node-positive, early breast cancer are at high risk of recurrence (up to 30% at 5 years) [1]. Previously, the monarchE trial (NCT03155997) showed a sustained benefit of 2 years of adjuvant abemaciclib to endocrine therapy in patients with HR-positive/HER2-negative, node-positive, high-risk early breast cancer with a hazard ratio of 0.68 for both invasive disease-free survival and distant relapse-free survival [2]. Molecular profiling was preformed to evaluate potential biomarkers that might predict the benefit of adjuvant abemaciclib in this patient population. Prof. Nick Turner (The Royal Marsden Hospital and Institute of Cancer Research, UK) presented the results [3].

Molecular profiling was performed in a sub-cohort (n=1,400) of the intention-to-treat population of monarchE. Whole-exome sequencing on baseline was performed in 1,173 tumour samples, RNA expression (Oncotype DX) was determined in 1,190 tumour samples at baseline. Patient characteristics and abemaciclib benefit were consistent in these 3 subpopulations.

A consistent abemaciclib treatment benefit was found across all intrinsic molecular subtypes (luminal A, luminal B, HER2-enriched, and basal). Abemaciclib benefit was also achieved regardless of Oncotype DX risk score (≤25 vs >25). Of all oncogenic mutations and copy number alterations with a prevalence ≥9%, only MYC amplification was associated with less benefit of abemaciclib. “However, this observation is based on a small sample size,” Prof. Turner noted.

Prof. Turner concluded that “abemaciclib demonstrated a consistent benefit across all breast cancer-intrinsic molecular subgroups, for both high and low Oncotype DX risk scores, and for all most prevalent genomic alterations with the exception of MYC amplification. Future work will include the integration of additional exploratory and more comprehensive genomic and transcriptomic analyses with clinical outcomes from monarchE.”

1. Sheffield KM, et al. Future Oncol. 2022;18:2667-2682.
2. Harbeck NA, et al. Ann Oncol. 2023;34(suppl 2):S1256.
3. Turner N, et al. Genomic and transcriptomic profiling of primary tumors from patients with HR+, HER2-, node-positive, high-risk early breast cancer in the monarchE trial. Abstract GS03-06, SABCS 2023, 5–9 December, San Antonio, TX, USA.

 

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Posted on 11 January 202411 January 2024