Racial disparities in neutrophil counts among patients with metastatic breast cancer during treatment with CDK4/6 inhibitors.

PURPOSE: The three CDK4/6 inhibitors (CDK4/6i) approved for use in HR-positive/HER2-negative metastatic breast cancer (MBC), palbociclib, ribociclib, and abemaciclib, are generally well tolerated; however, neutropenia is a common toxicity. Within the general population, neutropenia has been shown to be more common in individuals of African descent. The landmark CDK4/6i trials in MBC lacked racial diversity in their patient populations. We aimed to assess the toxicity profiles of CDK4/6is in a racially diverse population. METHODS: We conducted a retrospective study at Montefiore Medical Center in patients with HR-positive/HER2-negative MBC prescribed CDK4/6i as first or subsequent line therapy between January 2015 and April 2020. Baseline characteristics and laboratory data at various treatment timepoints were collected. RESULTS: The final analysis included 182 patients, of whom 46% were Black. Baseline absolute neutrophil count (ANC) was lower in the Black vs. Non-Black cohort (p = 0.001) but the change in ANC from baseline (delta-ANC) was smaller in the Black cohort, and the ANC at different treatment timepoints was similar between groups. There was no difference in the rate of infection or number of dose delays/reductions between racial groups. We did not find any difference in PFS between Black and Non-Black groups, regardless of the presence of CDK4/6i-induced neutropenia. CONCLUSION: We analyzed toxicity profiles of 182 patients with HR-positive/HER2-negative MBC treated with CDK4/6i. Despite the lower baseline ANC seen in our Black cohort, treatment toxicities were similar between racial groups. Long-term outcomes with CDK4/6i therapy, measured by PFS, were similar between Black vs. Non-Black patients.

Facts and Perspectives: Implications of tumor glycolysis on immunotherapy response in triple negative breast cancer.

Triple negative breast cancer (TNBC) is an aggressive disease that is difficult to treat and portends a poor prognosis in many patients. Recent efforts to implement immune checkpoint inhibitors into the treatment landscape of TNBC have led to improved outcomes in a subset of patients both in the early stage and metastatic settings. However, a large portion of patients with TNBC remain resistant to immune checkpoint inhibitors and have limited treatment options beyond cytotoxic chemotherapy. The interplay between the anti-tumor immune response and tumor metabolism contributes to immunotherapy response in the preclinical setting, and likely in the clinical setting as well. Specifically, tumor glycolysis and lactate production influence the tumor immune microenvironment through creation of metabolic competition with infiltrating immune cells, which impacts response to immune checkpoint blockade. In this review, we will focus on how glucose metabolism within TNBC tumors influences the response to immune checkpoint blockade and potential ways of harnessing this information to improve clinical outcomes.