Combination of Abemaciclib and Trastuzumab Improves OS in HR+, HER2+ Advanced Breast Cancer

Adding abemaciclib to trastuzumab improved overall survival in women with with hormone receptor–positive, HER2-positive advanced breast cancer, according to new findings discussed at the 2022 ESMO Congress.

Abemaciclib (Verzenio) plus trastuzumab (Herceptin), with or without fulvestrant, improved overall survival (OS) in women with hormone receptor–positive, HER2-positive advanced breast cancer vs standard-of-care chemotherapy plus trastuzumab, according to data presented at the 2022 European Society for Medical Oncology Congress (ESMO).1

Fabrice André, MD, PhD, director of research at Gustave Roussy in Villejuif, France, presented the data from a prespecified final analysis from the phase 2 monarcHER trial (NCT02675231) at the congress.

As of the data cutoff on March 31, 2022, median OS in arms A (experimental regimen plus fulvestrant), B (experimental regimen alone), and C (control therapy) were 31.1 months (arms A vs C: HR, 0.71; 95% CI, 0.48-1.05; 2-sided P value = .086), 29.2 months (arms B vs C: HR, 0.84; 95% CI, 0.57-1.23; 2-side P value = .365), and 20.7 months, respectively. In comparing arms A and C, the triplet regimen with the oral CDK4/6 inhibitor induced a statistically significant improvement in OS compared with trastuzumab plus chemotherapy.

Moreover, there was a consistent benefit observed with the pooled abemaciclib arms across all pre-specified subgroups.

An exploratory analysis of RNA sequencing of intrinsic subtypes showed that luminal subtypes of disease compared with non-luminal subtypes were associated with longer median progression-free survival (PFS; 8.6 months vs 5.4 months; HR, 0.54; 95% CI, 0.38-0.79) and OS (31.7 months vs 19.7 months; HR, 0.68; 95% CI, 0.46-1.00).

André said there were no new adverse events (AEs).

In the randomized, multicenter, open-label phase 2 trial, patients were randomized 1:1:1 to receive either abemaciclib plus fulvestrant and trastuzumab (arm A; n = 79), abemaciclib plus trastuzumab (arm B; n = 79), or trastuzumab plus standard-of-care chemotherapy (arm C; n = 79) at doses of:

  • 150 mg abemaciclib twice daily on days 1 through 21 of a 21-day cycle;
  • 8 mg/kg of intravenous trastuzumab on cycle 1, day 1, followed by 6 mg/kg on day 1 of each subsequent 21-day cycle
  • 500 mg intramuscular fulvestrant on days 1, 15, and 29 and once every 4 weeks thereafter.

Investigator-assessed PFS in the intent-to-treat population (arm A vs C, then arm B vs C) served as the primary end point. Secondary end points included OS, overall response rate, patient-reported outcomes, and pharmacokinetics. Safety was also assessed in any patient who received at least 1 dose of study treatment.

Patients were eligible if they were 18 years or older; had hormone receptor–positive, HER2-positive advanced breast cancer with unresectable, locally advanced, recurrent or metastatic disease; had an ECOG performance status of 0 or 1; had previously received at least 2 HER2-directed targeted therapies for advanced disease; and has prior ado-trastuzumab emtansine (T-DM1; Kadcyla) and taxane therapy.

In the previously reported data, after a median follow-up of 19.0 months (range, 14.7-25.1), treatment on arm A compared with arm C induced superior median PFS at 8.3 months (95% CI, 5.9-12.6) vs 5.7 months (95% CI, 5.4-7.0) with control therapy for a reduction in the risk for disease progression or death of 33% (HR, 0.67; 95% CI, 0.45-1·00; P = .051).2

The most common grade 3/4 treatment-emergent adverse event (TRAE) in arms A, B, and C, was neutropenia (27% vs 22% vs 26%, respectively). In arm A, the most common serious AEs included pyrexia (4%), diarrhea (3%), urinary tract infection (3%), and acute kidney injury (3%).


1) Andre F, Nadal JC, Denys H, et al. Final overall survival (OS) for abemaciclib plus trastuzumab +/- fulvestrant versus trastuzumab plus chemotherapy in patients with HR+, HER2+ advanced breast cancer (monarcHER): A randomized, open-label, phase II trial. Ann Oncol. 2022;33(suppl 7):LBA18. doi:10.1016/j.annonc.2022.08.013

2) Tolaney SM, Wardley AM, Zambelli S, et al. Abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in women with hormone receptor-positive, HER2-positive advanced breast cancer (monarcHER): a randomised, open-label, phase 2 trial. Lancet Oncol. 2020;21(6):763-775. doi:10.1016/S1470-2045(20)30112-1