Messaggi chiave
- È stata condotta una revisione sistematica e metanalisi della letteratura volta a esaminare efficacia e sicurezza di abemaciclib in combinazione con la terapia endocrina nel trattamento del carcinoma mammario (BC) HR+/HER2- in stadio avanzato o metastatico.
- Utilizzando le banche dati PubMed, EMBASE, Cochrane Library e ClinicalTrials.gov (fino a dicembre 2023), sono stati individuati 22 studi idonei, per un totale di 14.010 pazienti. Dall’analisi dei dati aggregati è emerso che abemaciclib migliorava significativamente gli esiti di sopravvivenza libera da progressione (hazard ratio, 0,53; IC 95%, 0,48-0,59; p = 0,00; I2 = 0%), tasso di risposta complessiva (risk ratio [RR], 2,31; IC 95%, 1,93-2,75; p = 0,00; I2 = 0%) e sopravvivenza globale (RR = 0,76; IC 95%, 0,65-0,87; p = 0,001; I2 = 0%), a fronte però di un aumento del rischio di eventi avversi.
- Abemaciclib, soprattutto in associazione a fulvestrant, rappresenta un’opzione terapeutica efficace nel BC HR+/HER2- avanzato/metastatico, migliorando gli esiti di sopravvivenza. Tuttavia, il suo profilo di tossicità impone una certa cautela, particolarmente in pazienti naïve al trattamento.
Abstract
Objectives
- Breast cancer, particularly the hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) subtype, remains a major global health concern.
- Abemaciclib, a CDK4/6 inhibitor, has shown promising results in treating advanced cases.
- This study comprehensively assesses the efficacy and safety of abemaciclib in combination with endocrine therapy for HR+/HER2- advanced or metastatic breast cancer.
Methods
- Following PRISMA guidelines, a systematic review and meta-analysis was conducted.
- A thorough literature search was conducted on PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov til December 2023.
- Inclusion criteria encompassed randomized controlled trials and retrospective cohort studies reporting on abemaciclib in approved doses, either as monotherapy or in combination.
- Outcome assessments included progression-free survival (PFS), overall response rate (ORR), side effects/adverse effects (SE/AE), and overall survival (OS).
- Quality assessment utilized Cochrane’s revised risk of bias tool and Newcastle-Ottawa scale.
Results
- Pooled results of 22 studies involving 14,010 patients revealed that abemaciclib significantly improved PFS (hazard ratio = 0.53; 95% CI: 0.48-0.59; p = 0.00; I2 = 0%), ORR (risk ratio = 2.31; 95% CI: 1.93-2.75; p = 0.00; I2 = 0%), and OS (risk ratio = 0.76 (95% CI: 0.65-0.87; p = 0.001; I2 = 0%).
- However, abemaciclib increased the risk of adverse events in the fulvestrant and nonsteroidal aromatase inhibitor (NSAI) combinations, respectively.
Conclusions
- Abemaciclib, particularly in combination with fulvestrant, emerges as an effective therapeutic option for HR+/HER2- advanced or metastatic breast cancer, improving PFS and OS.
- The higher toxicity profile warrants cautious use, especially in treatment-naive patients.