Messaggi chiave
- In MONARCH 3, abemaciclib aggiunto a un inibitore delle aromatasi non steroideo (NSAI) ha prodotto un beneficio significativo in sopravvivenza libera da progressione (PFS) quando somministrato upfront in pazienti in post-menopausa con carcinoma mammario avanzato (aBC) HR+/HER2-. Si illustrano di seguito i risultati appena pubblicati dell’analisi finale prespecificata della sopravvivenza globale (OS).
- A un follow-up mediano di 8,1 anni, con 198 eventi di OS nel braccio abemaciclib e 116 nel braccio placebo, l’OS mediana è risultata pari a 66,8 vs 53,7 mesi (HR, 0,804; IC 95%, 0,637-1,015; p = 0,0664) nella popolazione intent-to-treat e a 63,7 vs 48,8 mesi (HR, 0,758; IC 95%, 0,558-1,030; p = 0,0757) nel sottogruppo con malattia viscerale. È stato inoltre osservato un prolungamento numerico della sopravvivenza libera da chemioterapia e un mantenimento del beneficio in PFS precedentemente dimostrato.
- I risultati finali dello studio suggeriscono un miglioramento clinicamente significativo dell’OS con NSAI + abemaciclib rispetto a placebo in pazienti con aBC HR+/HER2- non precedentemente trattate nel setting avanzato; tuttavia, non è stata raggiunta la significatività statistica.
Abstract
Background
- In MONARCH 2, the addition of abemaciclib to fulvestrant significantly improved both progression-free survival (PFS) and overall survival (OS) in patients with HR+, HER2- advanced breast cancer (ABC) with disease progression on prior endocrine therapy (ET).
- In MONARCH 3, the addition of abemaciclib to a nonsteroidal aromatase inhibitor (NSAI) as initial therapy for HR+, HER2- ABC significantly improved PFS. Here, we present the prespecified final OS results for MONARCH 3.
Patients and Methods
- MONARCH 3 is a randomized, double-blind, phase 3 study of abemaciclib plus NSAI (anastrozole or letrozole) versus placebo plus NSAI in postmenopausal women with HR+, HER2- ABC without prior systemic therapy in the advanced setting.
- The primary objective was investigator-assessed PFS; OS was a gated secondary endpoint, and chemotherapy-free survival (CFS) was an exploratory endpoint.
Results
- A total of 493 women were randomized 2:1 to receive abemaciclib plus NSAI (n = 328) or placebo plus NSAI (n = 165).
- After a median follow-up of 8.1 years, there were 198 OS events (60.4%) in the abemaciclib arm and 116 (70.3%) in the placebo arm (hazard ratio, 0.804; 95% confidence interval [CI], 0.637-1.015; p = 0.0664, non-significant).
- Median OS was 66.8 versus 53.7 months for abemaciclib versus placebo. In the subgroup with visceral disease (sVD), there were 113 OS events (65.3%) in the abemaciclib arm and 65 (72.2%) in the placebo arm (hazard ratio, 0.758; 95% CI, 0.558-1.030; p = 0.0757, non-significant).
- Median OS was 63.7 months versus 48.8 months for abemaciclib versus placebo.
- The previously demonstrated PFS benefit was sustained, and CFS numerically improved with the addition of abemaciclib. No new safety signals were observed.
Conclusions
- Abemaciclib combined with an NSAI resulted in clinically meaningful improvement in median OS (ITT: 13.1 months; sVD: 14.9 months) in patients with HR+ HER2- ABC; however, statistical significance was not reached.