A real-world analysis shows “meaningful” overall survival benefits when a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor is added to endocrine therapy for older women with HR-positive/HER2-negative metastatic breast cancer (MBC).
Three years after starting first-line treatment, overall survival rates were 49% with endocrine therapy alone, vs 73% with endocrine therapy plus a CDK4/6 inhibitor — findings largely consistent with clinical trial data.
Treatment with endocrine therapy alone “should have a limited role in early lines of therapy for patients with HR+/HER2- MBC,” the researchers conclude.
The study was published online earlier this month in the journal Cancer.
The US Food and Drug Administration has approved the CDK4/6 inhibitors palbociclib, abemaciclib, and ribociclib for HR-positive/HER2-negative MBC in first and advanced therapy lines. The approval was based on phase 3 randomized controlled trial data.
Yet gaps in evidence remain regarding survival outcomes in real-world settings for patients starting treatment with a CDK4/6 inhibitor, particularly for patients aged 65 and older, who typically aren’t included in randomized clinical trials.
To address these gaps, Ravi Goyal, PhD, with the College of Pharmacy, University of Houston, and colleagues conducted a retrospective cohort study using the Survey Epidemiology and End Results (SEER) Medicare database.
Goyal and co-authors identified 630 Medicare patients with HR-positive/HER2-negative MBC for whom first-line treatment was initiated within 12 months of diagnosis. Patients received either endocrine therapy alone (461 patients) or endocrine therapy plus a CDK4/6 inhibitor (169 patients), most commonly palbociclib.
The median duration of follow-up from the start of treatment was 24 months in the endocrine therapy alone group and 30 months in the combination therapy group.
In a Kaplan-Meier analysis, the overall survival rate at 3 years after starting first-line treatment was 73% for the combination therapy group, vs 49% for the endocrine therapy group (P < .0001). Median overall survival from first-line therapy was not estimable in the endocrine therapy plus CDK4/6 inhibitor group; it was 34.8 months in the endocrine therapy only group.
In multivariable Cox regression models, first-line dual therapy was independently associated with 41% lower rate of death in comparison with endocrine therapy alone (adjusted hazard ratio [aHR], 0.59).
Goyal and colleagues also performed a separate analysis of 206 patients for whom treatment was initiated in the second line; 88 received endocrine therapy alone, and 118 received endocrine therapy plus CDK4/6 inhibitor therapy.
In this setting, a similar benefit of dual therapy was observed. The 3-year overall survival rate was 68% for the combination group, vs 50% for endocrine therapy alone (P = .0051). Median overall survival with second-line therapy was not estimable for the combination group; it was 30.9 months for the endocrine therapy group.
In the second line, multivariable Cox regression analysis showed that combination therapy was associated with a nearly 58% lower rate of death in comparison with endocrine therapy alone (aHR, 0.42).
The co-authors of an editorial in Cancer explain that the combination of a CDK4/6 inhibitor and endocrine therapy has become the “preferred first-line approach” in the management of HR-positive/HER2-negative MBC.
The editorialists note that an overall survival benefit of similar magnitude from endocrine therapy plus a CDK4/6 inhibitor has also been reported in a recent real-world study of palbociclib and letrozole.
The work of Goyal and colleagues provides “confirmatory real-world evidence observed in clinical trials for endocrine sensitive, de novo, metastatic [breast cancer] in an older population,” write editorialists Dario Trapani, MD, and Erica Mayer, MD, with Dana-Farber Cancer Institute, Boston.
The study had no specific funding. The authors and Trapani have disclosed no relevant financial relaitonships. Mayer has consulted for Lilly, Novartis, Gilead, AstraZeneca, and Diaccurate.
Cancer. Published online February 9, 2023. Abstract, Editorial
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