Examining Different Sequence Effects of CDK4/6 Inhibitor Combinations on Actual Real-World Outcomes of Treatment in Patients with Hormone Receptor–Positive and HER2-Negative Metastatic Breast Cancer

2020 Year in Review - Breast Cancer - Breast Cancer

While progression-free survival was similar, overall survival was better in CDK4/6 inhibitor combinations as first-line therapy followed by everolimus combinations and chemotherapy.

In a poster presentation, Silvia Comis, MD, Senior Medical Director, Oncology-Therapeutic Science and Strategy, IQVIA, Milan, Italy, discussed clinical trials in which CDK4/6 inhibitors have shown clear benefits in terms of progression-free survival and overall survival. Despite this growing body of evidence suggesting their benefit in the clinical setting, best practices remain unresolved and persistent issues exist, such as optimal sequencing with other therapies when treating patients with hormone receptor–positive, HER2-negative metastatic breast cancer. Therefore, it is critically important to examine the range of CDK4/6 inhibitor combinations used in patients with hormone receptor–positive, HER2-negative metastatic breast cancer, in light of real-world evidence.

Researchers used IQVIA’s oncology US electronic health records for the fourth quarter of 2015 to the first quarter of 2020 to identify 16,017 patients with metastatic breast cancer aged ≥18 years with hormone receptor–positive, HER2-negative disease. Based on different sequential use of drugs, patients were organized into 4 cohorts. In the first cohort, hormonal therapy was used as first-line therapy followed by everolimus combinations, CDK4/6 inhibitor combinations, and chemotherapy. In the second cohort, CDK4/6 inhibitor combinations were used as first-line therapy, followed by everolimus combinations and chemotherapy. In the third cohort, everolimus combinations were used as first-line therapy followed by CDK4/6 inhibitor combinations and chemotherapy. In the fourth cohort, chemotherapy was used as first-line therapy as well as subsequent therapy.

Patient outcomes were analyzed for each cohort: progression (defined as time to next treatment), progression-free survival (defined as time to next treatment or death), and overall survival.

Statistically significant results between the first and second cohorts, generated by a test of proportions which demonstrated that more patients tend to live longer after they have been treated with CDK4/6 inhibitor combinations as first-line therapy, as shown by the second cohort at 80% compared with the first cohort at 87%. Due to the small total number of patients in the third cohort, statistical significance was not revealed.

On comparison between cohorts, more patients died in the fourth cohort in which chemotherapy was used as first-line therapy and subsequent therapy. Across cohorts, the median progression-free survival observed for CDK4/6 inhibitor combinations was 13.5 months.

The investigators concluded that based on this retrospective analysis, overall survival was better in the second cohort (CDK4/6 inhibitor combinations used as first-line therapy, followed by everolimus combinations and chemotherapy) when compared with other cohorts. However, progression-free survival during CDK4/6 inhibitor combinations was comparable. Future studies may focus on cohort demographics along with propensity score matching based on other variables and detailed CDK4/6 inhibitor combination analysis that may clarify these results.

Source: Comis S, Kandasamy T, Wu C, et al. Real-world evidence of CDK4/6 inhibitor combination effects on assessing outcome with different sequence of treatment among adult patients with HR+ and HER2- metastatic breast cancer. Ann Oncol. 2020;31(4_suppl). Abstract 307P.

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Last modified: July 22, 2021