Messaggi chiave
- È stata condotta un’analisi post-hoc di MONARCH 2, lo studio di fase 3 su fulvestrant ± abemaciclib in pazienti con carcinoma mammario avanzato (ABC) HR+/HER2- in progressione a terapia endocrina. Obiettivo dell’analisi era valutare l’associazione dei valori pretrattamento di rapporto neutrofili/linfociti (NLR) e conta linfocitaria assoluta (ALC) con gli esiti di efficacia.
- In entrambi i bracci, sopravvivenza libera da progressione (PFS) e sopravvivenza globale (OS) sono state numericamente più lunghe nei sottogruppi con NLR basale basso vs alto e ALC alta vs bassa. Inoltre, un NLR pretrattamento <2,5 è risultato essere un fattore prognostico di PFS e OS nel modello multivariato. Il beneficio dell’aggiunta di abemaciclib si è mantenuto a prescindere dai valori di NLR. Non sono state osservate differenze significative negli esiti di sicurezza.
- Nel complesso, tali dati suggeriscono che il rapporto neutrofili/linfociti può essere un utile marcatore prognostico nella popolazione con ABC HR+/HER2- avviata a trattamento con abemaciclib, in assenza però di qualsiasi significato predittivo di risposta alla terapia.
Abstract
Background
- Established prognostic factors for treatment response to cyclin-dependent kinases 4 and 6 inhibitors are currently lacking. We aimed to investigate the relationship of pretreatment neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) to abemaciclib outcomes.
Patients and methods
- This was a post hoc analysis of data from MONARCH 2, a phase III study of abemaciclib or placebo plus fulvestrant in hormone-receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer that progressed on endocrine therapy.
- Patients were divided into high and low categories based on baseline NLR (cutoff: 2.5) and ALC (cutoff: 1.5 × 109/L).
- The association of baseline NLR and ALC with progression-free survival (PFS) and overall survival (OS) was explored using Cox models and Kaplan-Meier estimates.
- Tumor response and safety were also examined.
Results
- NLR and ALC data were available for 645 patients (abemaciclib: N = 426; placebo: N = 219). Low-baseline NLR or high-baseline ALC was consistently associated with positive PFS and OS trends; low-baseline NLR subgroups also showed trends for better response.
- The abemaciclib treatment effect against placebo was observed regardless of baseline NLR or ALC. Univariate analyses showed baseline NLR and ALC were prognostic of PFS and OS.
- Baseline NLR remained significant in the multivariate model (P < 0.0001).
- No unexpected differences in safety were observed by baseline NLR or ALC.
Conclusion
- Baseline NLR was independently prognostic of PFS and OS. Low-baseline NLR was associated with numerically better efficacy outcomes, but the benefit of adding abemaciclib to fulvestrant was similar irrespective of baseline NLR status.