Final Results of NeoMONARCH: A Phase 2 Neoadjuvant Study of Abemaciclib in Postmenopausal Women with HR-Positive, HER2-Negative Breast Cancer

Abemaciclib is a selective oral inhibitor of CDK4 and CDK6. Dosed on a continuous schedule, abemaciclib showed evidence of antitumor clinical activity in patients with metastatic breast cancer (MBC) in monotherapy or in combination with a nonsteroidal aromatase inhibitor or fulvestrant.^1,2 NeoMONARCH is a phase 2 trial in women with stage I-IIIB, hormone receptor (HR)-positive, HER2-negative MBC, evaluating neoadjuvant treatment with abemaciclib plus anastrozole (ANZ). As previously reported, NeoMONARCH met its primary end point, showing that abemaciclib, alone or in combination with ANZ, significantly reduced Ki67 expression compared with ANZ alone after 2 weeks of treatment.³ The final results of this study were presented at SABCS 2017.

In this study, 224 patients were randomized (1:1:1) and 223 were treated for 2 weeks with abemaciclib (150 mg orally every 12 hours) plus ANZ (1 mg orally/day), abemaciclib alone, or ANZ alone.⁴ Then, all patients were treated for 14 weeks with the combination of abemaciclib plus ANZ. The primary objective was change in Ki67 from baseline to week 2. Secondary objectives evaluated after week 16 of treatment were radiologic, pathologic, and clinical responses; safety; and pharmacokinetics of abemaciclib and ANZ.

The Table shows subgroup analyses of percent change in Ki67 from baseline to week 2 by disease stage, baseline lymph node (LN) involvement, tumor grade, and tumor size in the Ki67 evaluable population (baseline Ki67 ≥5%) comparing the combination with ANZ alone.

A total of 167 patients completed treatment, at which time response rates were radiologic in 46.4% (all patients), caliper in 53.6% (all patients), and pathologic complete response in 3.7% (patients who completed breast cancer surgery assessment).

The most common adverse events (AEs) were diarrhea, constipation, and nausea. Treatment discontinuation due to AEs was low (7.6%). PIK3CA mutation status had no effect on Ki67 expression change from baseline to 2 weeks in response to the combination or abemaciclib, compared with ANZ alone. No analysis was performed on ESR1 mutation status for the outcome of Ki67 change, because of the small number of mutation-positive patients.

The authors concluded that abemaciclib plus ANZ is a significantly more effective treatment than ANZ alone, with manageable toxicities in patients with HR-positive, HER2-negative early breast cancer. The change in Ki67 by abemaciclib was not associated with disease stage, baseline LN involvement, tumor grade, tumor size, or PIK3CA mutation status.

Table. Subgroup Analyses of Ki67-Evaluable Population: Percent Change in Ki67 from Baseline to Week 2

Table. Subgroup Analyses of Ki67-Evaluable Population: Percent Change in Ki67 from Baseline to Week 2

References

1. Dickler MN, et al. Clin Cancer Res. 2017;23:5218-5224.
2. Sledge GW Jr, et al. J Clin Oncol. 2017;35:2875-2884.
3. NeoMONARCH Study Group. Cancer Discov. 2017;7:119-120.
4. Hurvitz MM, et al. SABCS 2017. Abstract PD5-01.