Incidence and severity of neutropenia in patients treated with cyclin-dependent kinase 4/6 inhibitors (CDKi) for metastatic breast cancer.

Abstract

e13036 Background: Palbociclib (P), ribociclib (R), and abemaciclib (A) are FDA approved CDKi used in combination with endocrine therapy for first- and second-line treatment of metastatic breast cancer. Neutropenia is a commonly encountered adverse effect with these agents. This analysis aimed to identify the incidence and severity of neutropenia in patients receiving CDKis. Methods: This retrospective, observational study used administrative data from the Optum’s de-identified Clinformatics® Data Mart Database (January 2016-June 2020) to identify patients treated with P, R, or A and who had at least two ICD-9 or ICD-10 diagnosis codes for breast cancer separated by >30 days. Using claims, neutropenia was defined as either one inpatient diagnosis code or 2 outpatient diagnosis codes from the time of the patient’s first CDKi prescription claim to the time of the last claim plus 42 days. For the subset of patients who had laboratory results during their period of treatment with CDKi, neutropenia was defined as an absolute neutrophil count (ANC) <1500 and severe neutropenia as ANC <500. Descriptive statistics and logistic regression models were used to characterize the population and to identify risk factors for development of neutropenia. Results: Of the total of 8,158 included patients, 82% were treated with P, 4.1% with R, 7.5% with A, and 6.4% with more than one CDKi. Patient age ranged from 28 to 91 years (median= 68 years). Median follow up from initiation of CDKi until the end was 194 days. 17.5% patients had ICD claims indicating neutropenia but only 1.6% were hospitalized with a diagnosis of neutropenia. Neutropenia codes were observed in 31.6% patients treated with P, 24.6% patients treated with R, and 15.6% patients treated with A. Among the 4766 patients who had laboratory results, 81% were treated with P, 4% with R, 7% with A, and 8% with more than one CDKi. 31.6% of patients had neutropenia defined by ANC < 1500. Severe neutropenia was seen in 10.8% of patients treated with P, 5.7% of those treated with R, and 5% of those treated with A. In a logistic regression model among the patients with lab results, patients treated with P had increased odds of neutropenia compared to those treated with A (OR 1.84, 95% CI 1.40-2.43) but patients treated with R vs A did not (OR 1.46, 95% CI 0.95-2.25). Asian and Hispanic patients had higher odds of neutropenia (OR 1.7, 95% CI 1.2-2.4, OR 2.1, 95% CI 1.8-2.6, respectively) compared to Whites, but Black patients had lower risk than White patients (OR 0.8, 95% CI 0.6-0.9). Conclusions: Neutropenia remains a common side effect of CDKis, although the frequency of severe neutropenia is low. Of the three CDKis, P was associated with the highest rate of neutropenia.