Racial disparities in overall survival after the introduction of cyclin-dependent kinase 4/6 inhibitors for patients with hormone receptor-positive, HER2-negative metastatic breast cancer

Abstract

Purpose: CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy have improved HR + /HER2- metastatic breast cancer (MBC) outcomes. However, it is still unclear whether the response to CDK4/6i is similar for all races. Therefore, we aimed to assess overall survival (OS) trends stratified by race in patients with HR + /HER2- MBC after the approval of CDK4/6i, as part of the standard of care, in 2015.

Methods: We performed a population-based study using the SEER database. Patients with HR + /HER2- MBC were divided into two time-based cohorts: 1) pre-CDK4/6i era (diagnosed in 2011-2013) and 2) post-CDK4/6i era (diagnosed in 2015-2017). We used propensity score matching and identified 2,684 patients in each cohort that matched in several characteristics. Kaplan-Meier methods were used to estimate 2-year OS. Association between cohort and OS was evaluated using marginal Cox proportional hazards models with robust sandwich variance estimator. We conducted competing risk analysis to estimate the risk of breast cancer death in both cohorts.

Results: The 2-year OS rate was 65% for the post-CDK4/6i era and 62% for the pre-CDK4/6i era (stratified log-rank p = 0.025). The 2-year OS for non-Hispanic White (NHW) patients improved in the post-CDK4/6i era compared to the pre-CDK4/6i era (67% vs. 63%, p = 0.033). However, OS did not improve for non-Hispanic Black (NHB) (54% vs. 54%, p = 0.876) or Hispanic (67% vs. 65%, p = 0.617) groups. The risk of breast cancer death decreased in the post-CDK4/6i era as compared to the pre-CDK4/6i era (2-year risk of breast cancer death: 33% vs. 30%, p = 0.015); however, this effect was observed only in NHW (sHR 0.84, p = 0.005) women, but not in NHB (sHR 0.94, p = 0.630) or Hispanic (sHR 0.91, p = 0.550) women.

Conclusions: Our study confirms that outcomes for HR + /HER2- MBC have improved after CDK4/6i were introduced in 2015. However, this effect is primarily driven by the improved OS in NHW patients, without significant improvement in OS in NHB or Hispanics.

Keywords: CDK4/6 inhibitors; Metastatic breast cancer; Race; SEER; Survival.