Combining a CDK4/6 inhibitor (CDKI) with fulvestrant provides an overall survival (OS) benefit in patients with advanced, hormone receptor (HR)-positive, HER2-negative breast cancer, regardless of predicted endocrine sensitivity, according to research published in The Lancet Oncology.1
In a prior analysis of data from 7 phase 3 trials, researchers reported significantly longer progression-free survival with the addition of a CDKI to endocrine therapy in patients with advanced, HR-positive, HER2-negative breast cancer.2
In the current analysis, researchers analyzed OS using pooled data from 3 randomized, phase 3 trials — MONARCH-2 (ClinicalTrials.gov Identifier: NCT02107703), PALOMA-3 (ClinicalTrials.gov Identifier: NCT01942135), and MONALEESA-3 (ClinicalTrials.gov Identifier: NCT02422615).
The trials were designed to compare CDKIs — abemaciclib, palbociclib, or ribociclib — plus fulvestrant with placebo-fulvestrant. Data from the trials were submitted to the US Food and Drug Administration (FDA) before August 1, 2020, in support of marketing applications.
The analysis included 1960 patients across the 3 trials. Twelve patients were ultimately not treated, 1296 (66%) patients were randomly assigned to receive a CDKI plus fulvestrant, and 652 (33%) were assigned to receive placebo plus fulvestrant.
At a median follow-up of 43.7 months, the estimated hazard ratio (HR) for OS was 0.77 (95% CI, 0.68-0.88) across all 3 trials, favoring the CDKI group. The difference in estimated median OS between the treatment groups was 7.1 months.
Death was reported in 48% (n=935) of patients overall, including 45% (n=586) in the CDKI group and 54% (n=349) in the placebo group.
Among patients who received CDKIs or placebo plus fulvestrant as first-line systemic endocrine therapy (n=396), the median follow-up was 39.4 months. The estimated HR for OS was 0.74 (95% CI 0.52-1.07), which suggested a potential benefit in the CDKI group, although the confidence interval crossed 1.0.
It was not possible to calculate the difference in estimated median OS for the first-line patients, as the median OS was not reached in the CDKI group (95% CI, 50.9-not estimable) and was 45.7 months in the placebo group (95% CI, 41.7-not estimable).
In patients treated with CDKIs or placebo plus fulvestrant as second-line or later therapy (n=1552), the median follow-up was 45.1 months. The estimated HR for OS was 0.77 (95% CI, 0.67-0.89) favoring the CDKI group. The difference in estimated median OS was 7.0 months.
An OS benefit from the CDKIs was observed across several clinicopathological subgroups, including patients with progesterone receptor-positive or -negative disease, lobular histology, bone-only metastatic disease, liver metastases, and lung metastases.
“These findings support the existing standard of care of CDKIs plus fulvestrant for the treatment of patients with hormone receptor-positive, HER2-negative, advanced breast cancer,” the researchers wrote.
- Gao JJ, Cheng J, Prowell TM, et al. Overall survival in patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer treated with a cyclin-dependent kinase 4/6 inhibitor plus fulvestrant: A US Food and Drug Administration pooled analysis. Lancet Oncol. Published online October 14, 2021. doi:10.1016/S1470-2045(21)00472-1
- Gao JJ, Cheng J, Bloomquist E, et al. CDK4/6 inhibitor treatment for patients with hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer: A US Food and Drug Administration pooled analysis. Lancet Oncol. 2020;21(2):250-260. doi:10.1016/S1470-2045(19)30804-6