Of 23 included patients, 2 (8.7%) had a confirmed PR, which triggered ongoing enrollment for a second study stage (ClinicalTrials.gov Identifier: NCT02308020).

Five patients were not evaluable. The 2 patients with confirmed PR had completed 14 and 15 cycles of therapy. Consistent with other experience with abemaciclib therapy, gastrointestinal adverse events were frequent.

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In another poster session, Mark Boye, PhD, principal research scientist at Eli Lilly in Indianapolis, Indiana, presented data on the effects of patient-reported diarrhea and pain on patient-assessed fatigue during abemaciclib monotherapy.5

Data were collected from patients who were treated with abemaciclib in the phase 2 MONARCH 1 study (ClinicalTrials.gov Identifier: NCT02102490), which enrolled women with HR+/HER2-negative metastatic breast cancer that had progressed on endocrine therapy and 1 or 2 chemotherapy regimens.6

Grade 1 to 3 diarrhea, fatigue, and abdominal pain were identified as treatment-emergent adverse events (TEAEs) occurring in 90%, 65%, and 39% of patients, respectively.

Dr Boyes’ ASCO presentation detailed the extent to which diarrhea and pain contributed to patient fatigue, using the Brief Pain Inventory and the EORTC QLQ-C30 v3, which were administered throughout the study.

This analysis used all items and constructs from the 2 measures (except the memory and financial difficulty items of the EORTC QLQ-C30) and estimated the Structural Equation Model (SEM), as well as the direct and indirect effects of pain and diarrhea on fatigue.

On SEM, pain was a significant predictor of fatigue in cycle 2; diarrhea was, however, not a significant predictor of fatigue.

A fourth presentation, also by Dr Tolaney, described the study design of the phase 2 monarcHER study, which will evaluate a regimen of abemaciclib plus trastuzumab, with or without fulvestrant, compared with standard of care chemotherapy plus trastuzumab among women with HR+/HER2-positive advanced breast cancer.7

This study (ClinicalTrials.gov Identifier: NCT02675231) is recruiting patients, with a target enrollment of 225 patients.

Eligible patients will have received at least 2 HER2-directed therapies in the advanced disease settings and/or T-DM1 and a taxane in any setting.

The primary endpoint will be PFS; secondary endpoints include overall survival, ORR, duration of response, disease control rate, clinical benefit rate, safety, and tolerability.

When available, results of monarcHer should help to elucidate the role of abemaciclib among HER2-positive women with advanced breast cancer.


  1. Sledge GW, Toi M, Neven P, et al. MONARCH 2: abemaciclib in combination with fulvestrant in patients with HR+/HER2– advanced breast cancer who progressed on endocrine therapy. J Clin Oncol. 2017;35(suppl; abstract 1000).
  2. Sledge GW Jr, Toi M, Neven P, et al. MONARCH 2: abemaciclib in in combination with fulvestrant in women with HR+/HER2– advanced breast cancer who progressed while receiving endocrine therapy. J Clin Oncol. 2017 Jun 3. doi: 10.1200/JCO.2017.73.7585 [Epub ahead of print]
  3. Tolaney SM, Lin NU, Thornton D, et al. Abemaciclib for the treatment of brain metastases secondary to hormone receptor positive HER2 negative breast cancer. J Clin Oncol. 2017;35(suppl; abstract 1019).
  4. Lin NU, Lee EQ, Aoyama H, et al. Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol. 2015;16:e270-8.
  5. Boye M, Houghton K, Stull DE, Ainsworth C, Price GL. Estimating the effects of patient-reported outcome diarrhea and pain measures on PRO fatigue: data analysis from a phase II study of abemaciclib monotherapy, a CDK4 and CDK6 inhibitor, in patients with HR+/HER2– breast cancer after chemotherapy for metastatic disease—MONARCH 1. J Clin Oncol. 2017;35(suppl; abstract 1060).
  6. Dickler MN, Tolaney S, Rugo HS, et al. MONARCH 1, a phase 2 study of abemaciclib a CDK 4 and CDK 6 inhibitor, as a single agent, in patients with refractory HR+/HER2– metastatic breast cancer. Clin Cancer Res. 2017 May 22. doi: 10.1158/1078-0432.CCR-17-0754 [Epub ahead of print]
  7. Tolaney SM, Bourayou N, Goel S, Hossain A, Andre F. A phase II randomized study to compare abemaciclib plus trastuzumab with or without fulvestrant to standard of care chemotherapy plus trastuzumab in hormone receptor positive, HER2-positive advanced breast cancer (monarcHER). J Clin Oncol. 2017;35(suppl; abstract TPS1109).