Abemaciclib, a selective inhibitor of CDK4 & 6, dosed on a continuous schedule is approved for the treatment of HR+, HER2- ABC. In the intent-to-treat population, abemaciclib with fulvestrant (F) demonstrated improved progression-free survival (PFS) and objective response rate (ORR) compared to placebo (P) + F (16.4 vs 9.3 mos, HR: 0.553; P<.0000001; ORR in measurable disease 48.1 vs 21.3%; P<.001). ET resistance (ETR) were classified into primary ETR, which includes pts whose disease relapsed while receiving the first 2 years of (neo)adjuvant ET or progressed while receiving the first 6 mos of ET for ABC, and secondary ETR. Here, we compare the efficacy and safety of abemaciclib + F vs P + F in the primary and secondary ETR subgroups.
MONARCH 2 was a phase 3 randomized, double-blind, placebo-controlled study of abemaciclib + F vs P + F in pts with HR+, HER2- ABC that progressed on ET. Key eligibility criteria were previously discussed. Pts received orally administered abemaciclib 150 mg Q12H + 500 mg F (per label) or P + F. Pts were stratified by sensitivity to ET. Primary objective was investigator-assessed PFS. Secondary objectives included efficacy, safety and tolerability.
169 pts (25.3%) had primary ETR and 489 pts (73.1%) had secondary ETR. Key efficacy endpoints are summarized (Table). The most frequent adverse events in primary and secondary ETR population are similar. For primary ETR, abemaciclib + F vs P + F were diarrhea (87.3 vs 22.4%), neutropenia (43.6 vs 5.2%), nausea (41.8 vs 25.9%), abdominal pain (36.4 vs 13.8%), and anemia (31.8 vs 5.2%), respectively.Table: 329P
Summary of PFS and ORR in primary and secondary ETR population
|Primary Resistance||Secondary Resistance|
|Abemacilib + F||Placebo + F||Abemacilib + F||Placebo + F|
|Hazard Ratio [HR] (95% CI)||0.45 (0.31, 0.67)||0.59 (0.46, 0.75)|
|ORR in measurable disease, (%)||53.9||17.9||46.2||22.6|
Abemaciclib + F improved PFS and ORR in pts with primary and secondary ETR, and had a generally tolerable safety profile. Although pts with primary ETR typically have poor prognosis the benefit for abemaciclib + F was maintained in pts HR+, HER2- ABC.
Clinical trial identification
Legal entity responsible for the study
Eli Lilly and Company.
Eli Lilly and Company.
Y. Lin: Employee and stakeholder: Eli Lilly and Company. All other authors have declared no conflicts of interest.