More study details
The 5637 women who were enrolled in monarchE were divided into two cohorts:
Cohort 1, which included patients with four or more positive nodes, or those with up to three positive nodes and a tumor size ≥5 cm or grade 3 disease
Cohort 2, which included women with up to three positive nodes and a Ki-67 index ≥20% based on a standard assay
“Cohort 2 opened one year after Cohort 1 and enrolled 517 patients,” Rastogi said.
Regardless of cohort, the patients were randomly assigned in a 1:1 fashion to abemaciclib for 2 years plus endocrine therapy for 5 to 10 years, as clinically indicated, or endocrine therapy alone.
At the primary efficacy outcome analysis, 395 IDFS events had occurred in the intention-to-treat analysis. The median follow-up was 19.1 months, and 25.5% of patients had completed the 2-year treatment period. A further 58.2% were still on treatment.
The results showed 163 IDFS events had occurred with abemaciclib plus endocrine therapy vs 232 with endocrine therapy alone, to give a 2-year IDFS rate of 92.3% vs 89.3%, at a hazard ratio of 0.713 (P = .0009).
Moving on to the subgroup analysis, Rastogi added that there were “no statistically significant interactions observed, indicating a consistent treatment benefit across all groups.”
The researchers also looked at IDFS rates in patients from both cohorts with Ki-67 index ≥20%, again finding that abemaciclib plus endocrine therapy was associated with significantly fewer events than endocrine therapy alone.
There were 82 events with the combination treatment vs 115 with endocrine therapy, at a 2-year IDFS rate of 91.6% vs 87.1% and a hazard ratio of 0.691 (P = .0111).
DRFS also significantly improved with abemaciclib plus endocrine therapy vs endocrine therapy alone, at a 2-year DRFS rate of 93.8% vs 90% or a hazard ratio of 0.687 (P = .0009).
“Safety remained consistent with the known profile of abemaciclib,” Rastogi said, “and what was observed at the second interim analysis, [with] minimal increases in any grade and grade ≥3 treatment-related adverse events.”
The most common adverse events were diarrhea, fatigue, and neutropenia, which were largely grades 1 and 2.
Notably, 2.4% of combination therapy patients experienced a venous thromboembolic event of any grade vs 0.6% of endocrine therapy patients, while 2.9% and 1.2%, respectively, had any grade interstitial lung disease.
At least one dose hold because of an adverse event was reported by 59.5% of patients on abemaciclib plus endocrine therapy, while 42.5% had at least one dose reduction because of an adverse event. In both cases, the primary reason was diarrhea.
Finally, Rastogi said that “over half of the discontinuations of abemaciclib due to adverse events occurred during the first 5 months of treatment, with the highest number…in the first month.”
Ki-67 issues
During the press conference, Virginia Kaklamani, MD, codirector of SABCS and leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center, Texas, asked about the practicalities of the Ki-67 index.
She said that testing is “great when it’s centrally done, but what do we expect physicians to do when some institutions do it, some don’t, and obviously it’s not really validated in most institutions around the world?”
Rastogi replied that is a “great question,” adding “this is something that is going to have to be sorted as we continue to have discussions and get more granularity of what to do when abemaciclib is administered in that patient population.”
Carlos L. Arteaga, MD, codirector of SABCS and director of the Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas, Texas, added that “most of us think of 10% as a cutoff between high and low” for the Ki-67 index, rather than ≥20%.
He said that he knows it is “arbitrary” but he thinks of 20% as “extremely high” and asked whether the researchers would be able to conduct a retrospective analysis to look at Ki-67 as a gradient to determine “at what point it stops predicting.”
Rastogi replied that, at the time monarchE was developed, some of the international guidelines used a Ki-67 index ≥20% as the cutoff.
She also noted that, although Ki-67 index ≥20% was an entry criterion for cohort 2, cohort 1 patients also provided tissue after randomization, “and so we’ll be able to look at these types of questions with our translational research committee.”
This study was sponsored by Eli Lilly. Rastogi has financial ties to AstraZeneca, Genentech/Roche, and the study sponsor, Eli Lilly. Regan has ties to Lilly and multiple other pharmaceutical companies. Sledge has ties to Lilly and other companies. Osborne has ties to Lilly and other companies.
This article first appeared on Medscape.com.