CDK4/6 Inhibitors Significantly Improved OS in Women With Advanced Breast Cancer, Studies Show

Women with hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative advanced breast cancer have improved overall survival (OS) when they were treated with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor plus fulvestrant, according to 2 abstracts presented at the European Society of Medical Oncology 2019 Congress.

MONARCH 2 analyzed the use of abemaciclib plus fulvestrant in pre- or perimenopausal and postmenopausal women with advanced endocrine therapy—resistant HR-positive, HER2-negative advanced breast cancer.¹ Data presented at the meeting 2 years ago had shown a significant improvement in progression-free survival, and this new data on overall survival showed a statistically significant and clinically meaningful improvement, according to first author George W. Sledge Jr, MD, of Stanford University School of Medicine.

MONARCH 2 included 669 patients who were randomized 2:1 to receive either abemaciclib and fulvestrant or placebo and fulvestrant. A total of 338 deaths were observed in the intention to treat population with a median OS of 46.7 months among the abemaciclib group compared with 37.3 months for the placebo group.

“The main take-home message from this study—and from other similar studies—is that CDK4/6 inhibitors significantly prolong the time patients remain in remission and significantly improve overall survival,” Sledge said in a statement. “Therefore, it is very reasonable to think of these as standard of care options for patients with metastatic breast cancer."

In the MONALEESA-3 trial, researchers found that first-line and second-line treatment with ribociclib and fulvestrant significantly improved OS in postmenopausal women with HR-positive, HER2-negative advanced breast cancer. Both women who had not previously been treated with hormonal therapy and those who had become resistant to endocrine therapy benefited from the regimen.

The patients were randomized 2:1 to receive ribociclib plus fulvestrant or placebo plus fulvestrant in the first-line and second-line settings. As of June 3, 2019, the data cutoff date, 153 patients were still on treatment and 34.5% of patients taking ribociclib and 44.6% of patients on the placebo had died. The median OS for patients taking ribociclib was statistically significantly longer across all subgroups.

The findings upend the traditional thinking that patients should first be treated with endocrine therapy and a CDK4/6 inhibitor should be saved for when endocrine therapy no longer works, according to study author Dennis J. Slamon, MD, PhD, of the University of California, Los Angeles.

"The data from Monaleesa-3 clearly show that if postmenopausal patients receive this right up front there is a very significant benefit—not only in progression-free survival, which had already been published—but now with this new report in overall survival—which is the hardest end point to reach, and the most important one in terms of making an impact on the disease,” he said.

References

1. Sledge G, Toi M, Neven P, et al. MONARCH 2: overall survival of abemaciclib plus fulvestrant in patients with HR+, HER2- advanced breast cancer. Ann Oncol. 2019;30(Suppl 5):v851-v934. doi: 10.1093/annonc/mdz394.

2. Slamon DJ, Neven P, Chia S, et al. Overall survival (OS) results of the phase III MONALEESA-3 trial of postmenopausal patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor 2-negative (HER2−) advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB). Ann Oncol. 2019;30(Suppl 5):v851-v934. doi: 10.1093/annonc/mdz394.