Among those recently diagnosed with BC, approximately 6% of cases have already metastasized, resulting in a 5-year survival rate of 29.0%. Recommended treatment options include the use of cyclin-dependent kinase (CDK) 4/6-inibitors in combination with endocrine therapy (ET). Among the CDK 4/6-inhibitors, palbociclib in combination with an aromatase inhibitor (AI) is approved for use as first-line treatment for hormone receptor–positive (HR+)/hormone epidermal growth factor factor 2 (HER2)–negative MBC; with fulvestrant in patients with MBC who have progressed on ET; and in men with HR+/HER2-MBC.

Previous comparative effectiveness analyses of CDK 4/6-inhibitors in MBC have been limited by small sample sizes, short follow-up periods, single-type ET use (letrozole only), and lack of male MBC subjects. To address these concerns, investigators conducted a real-world retrospective analysis of electronic health records from February 3, 2015, to March 31, 2020, from the Flatiron Health Analysis Database, a longitudinal database of patient data from over 280 cancer clinics in the United States.

The primary outcome of the study was overall survival (OS), which was defined as the number of months from the start of treatment with palbociclib plus an AI or an AI alone until death. The secondary outcome was real-world progression-free survival (rwPFS), which was the number of months from the start of treatment with palbociclib and an AI or with an AI alone to the date of the first documented real world progressive disease or death due to any cause, whichever occurred first.

There were differences between the treatment groups in performance status, de novo MBC status, comorbidity scores, and number of metastatic sites. To compensate for confounders in the observational study, the investigators used stabilized inverse probability treatment weighing (sIPTW) and propensity score matching as a sensitivity analysis to assess the robustness of the sIPTW. The combination of these measures produces a pseudo population in which confounders are equally distributed between the group of interest and the unexposed group.

A total of 2,888 (2,859 female and 29 male) patients with MBC were included in the study, including 1,324 who were on the CDK 4/6-inhibitor and an AI and 1,564 that were on an AI monotherapy; 10 men were on the combination regimen and 19 were on an AI only. The median age was 70 years, with 30% having visceral disease (i.e., metastatic disease in the lungs and/or liver). The median duration of follow-up was approximately 2 years for both groups (23.9 months in the palbociclib-plus-AI group and 24.5 months in AI-only group).

Those in the palbociclib and AI group were 24% significantly less likely to die versus the AI monotherapy group (after adjusting for sIPTW), with a median OS of 49.1 months in the combination group versus 43.2 months in the AI group (hazard ratio [HR] 0.76: 95% CI; 0.65-0.87, P <.0001). A similar advantage for combination therapy was seen in OS after propensity score matching with a median OS of 57.8 months in the palbociclib-plus-AI group versus 43.5 months in the AI group (HR 0.72: 95% CI; 0.62-0.83, P <.0001).

There was also a significant difference in rwPFS with rwPFS of 19.3 months in the combination group versus 13.9 in the AI monotherapy group (after adjusting for sIPTW) (HR 0.70: 95% CI; 0.62-0.78, P <.0001). This difference in rwPFS remained significant after propensity score matching for rwPFS at 19.8 months and 14.9 months for the combination versus monotherapy groups, respectively (HR 0.72; 95% CI, 0.63-0.82). Subgroup analyses showed similar benefit among different racial groups and types of metastases (visceral disease or bone only).

This study provides pharmacists with real-world evidence of the benefit of palbociclib and AI cotherapy in prolonging OS and rwPFS among both women and men with MBC.

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