The following article features coverage from the European Society for Medical Oncology (ESMO) 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

The CDK 4/6 inhibitor abemaciclib plus fulvestrant was associated with a median overall survival (OS) improvement of 9.4 months compared with fulvestrant alone among patients with HR-positive, ERBB2-negative (HR+, HER2-) advanced breast cancer who had progressed after prior endocrine therapy, regardless of menopausal status, according to findings from the randomized, placebo-controlled phase 3 MONARCH 2 study ( Identifier: NCT02107703). Results were presented at the European Society of Medical Oncology (ESMO) Congress 2019 in Spain and simultaneously published in JAMA Oncology.1,2 Abemaciclib also “substantially” prolonged time to subsequent chemotherapy, the authors reported.

With these findings, abemaciclib becomes the third CDK 4/6 inhibitor for which an OS benefit has been demonstrated for patients with advanced HR+, HER2- breast cancer. 

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“Results from the MONARCH 2 study presented 2 years ago3 showed significant improvement in progression-free survival [PFS] for patients treated with the combination of abemaciclib plus fulvestrant compared [with] fulvestrant alone,” said lead study author George Sledge, MD, of the Stanford University School of Medicine in Stanford, California, in an ESMO press release.4 “Now, with further follow-up, we have overall survival data showing a statistically significant and clinically meaningful improvement in overall survival with the combination.”

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MONARCH 2 enrolled 669 women between August 2014 and December 2015, 446 of whom were randomly assigned to receive fulvestrant (500 mg) plus placebo, while 223 were administered fulvestrant (500 mg) plus abemaciclib (150 mg every 12 hours). 

At a prespecified interim analysis of data for the intent-to-treat study population up to June 20, 2019, the median OS of the abemaciclib and placebo groups were 46.7 and 37.3 months, respectively (hazard ratio [HR], 0.757; 95% CI, 0.606–0.945; P =.01). Numeric improvements in OS were seen in subgroup analyses, including visceral disease status and primary resistant to prior endocrine therapy.

“Time to second disease progression (median, 23.1 months vs 20.6 months), time to chemotherapy (median, 50.2 months vs 22.1 months), and chemotherapy-free survival time (median 25.5 months vs 18.2 months) were also statistically significantly improved in the abemaciclib arm vs the placebo arm,” Dr Sledge said. “No new safety signals were observed for abemaciclib.”

Common grade 3/4 hematologic adverse events in the abemaciclib study group included neutropenia (29.9%), anemia (9.1%), and leukopenia (11.1%). Diarrhea was also common (14.5%), in most cases during the first 4 weeks of treatment. Diarrhea was effectively managed with loperamide and dose adjustments. After 1 year or more of treatment, new treatment-emergent diarrhea of any grade was reported for 28% of patients in the abemaciclib group and 11% of the placebo group.

“CDK 4/6 inhibitors significantly prolong the time patients remain in remission and significantly improve overall survival,” Dr Sledge concluded. “Therefore, it is very reasonable to think of these as standard of care options for patients with metastatic breast cancer.”

Disclosure: This study was funded by Eli Lilly and Company. For a full list of author disclosures, please refer to the original abstract.

Read more of Cancer Therapy Advisor‘s coverage of the ESMO annual meeting by visiting the conference page.


  1. Sledge GW, Toi M, Neven P, et al. MONARCH 2: Overall survival of abemaciclib plus fulvestrant in patients with HR+, HER2-advanced breast cancer. Presented at: ESMO Congress 2019; Madrid, Spain: September 8-12, 2017. Abstract LBA6.
  2. Sledge GW, Toi M, Neven P, et al. The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, ERBB2-negative breast cancer that progressed on endocrine therapy—MONARCH 2: A randomized clinical trial [published online September 29, 2019]. JAMA Oncol. doi: 10.1001/jamaoncol.2019.4782
  3. Sledge GW, Toi M, Nevin P, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017;35:2875-2884.
  4. European Society of Medical Oncology (ESMO). Two studies show CDK4/6 inhibitors improve overall survival in advanced breast cancer [press release]. Published September 29, 2019.