Older Breast Cancer Patients Fare Well With Combo Of CDK4/6 Inhibitor And AI

By Susan London


Combination therapy with a cyclin-dependent kinase (CDK) 4/6 inhibitor and an aromatase inhibitor (AI) has the same good efficacy but greater toxicity in women with hormone receptor (HR)–positive, HER2-negative advanced breast cancer who are aged 75 years or older, a pooled analysis of randomized controlled trials concluded.

Results reported in the Journal of Clinical Oncology showed that in this age-group, compared with an AI alone, the combination of a CDK 4/6 inhibitor with an AI reduced the risk of progression or death by 51%, similar to the 44% reduction seen among women younger than 75 years. At the same time, nearly 9 in 10 of the older group experienced grade 3 or 4 adverse events, relative to roughly 7 in 10 of the younger group.

“Compared with their younger counterparts, older patients derived similar benefit from treatment with a CDK4/6 inhibitor, worsened toxicity that could be managed with supportive care, and similar decline in quality-of-life measures regardless of the addition of a CDK4/6 inhibitor,” summarized Harpreet Singh, MD, a medical officer at the Food and Drug Administration and coinvestigators.

“As CDK4/6 inhibitors are incorporated into the standard of care for the initial treatment of HR-positive, HER2-negative MBC [metastatic breast cancer], this pooled analysis provides important efficacy, safety, and tolerability data for counseling older women who are considering use of AIs in combination with CDK4/6 inhibitors,” they wrote.
For the analysis, the investigators pooled data from three first-line randomized controlled trials – PALOMA-2, MONALEESA-2, and MONARCH-3 – among 1,827 postmenopausal women with HR–positive, HER2-negative locally advanced or metastatic breast cancer. The trials tested the addition of the CDK 4/6 inhibitors palbociclib (Ibrance), ribociclib (Kisqali), or abemaciclib (Verzenio), respectively, to an AI.

Overall, 10.8% of patients in the pooled cohort were aged 75 years or older. Among these older women, progression-free survival was better with a CDK4/6 inhibitor plus an AI, compared with that of an AI alone (median, 31.1 vs. 13.7 months; hazard ratio, 0.49). The benefit was statistically indistinguishable from that among women younger than 75 years (median, 27.6 vs. 14.9 months; hazard ratio, 0.56; P = .52 for interaction).

However, fully 88.8% of the older group experienced a grade 3 or 4 adverse event, compared with 73.4% of the younger group. And the former had higher rates of adverse events leading to dose reduction and/or interruption (81.6% vs. 71.1%) and discontinuation (32% vs. 12.1%).

Relative to younger counterparts and regardless of treatment arm, women aged 75 years or older experienced a more rapid deterioration of quality of life measures – mobility, self-care, and ability to perform usual activities – as assessed with the EuroQol 5-dimension (EQ-5D) questionnaire.


A study strength was the pooling of data, which enabled identification of sizable groups of women aged 70 years and older and aged 75 years and older, relatively few of whom were included in individual trials, Dr. Singh and coinvestigators noted.

“Ongoing efforts to modernize eligibility criteria for oncology clinical trials should result in a greater body of data in the older postmenopausal women who represent the majority of patients in the United States with HR-positive, HER2-negative MBC,” they concluded. “Increased inclusion of older patients in clinical trials will help to inform clinicians and patients about how to consider and incorporate new therapies into their treatment plans.”

Dr. Singh disclosed no relevant conflicts of interest. The study did not receive any specific funding.

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