Category: Fellows Posters
Cyclin-dependent kinase (CDK) 4/6 inhibitors have been shown to improve survival rates for patients diagnosed with metastatic breast cancer. Adverse events are common, but often manageable.
The objective of our study was to analyze laboratory toxicities of cyclin inhibitors (palbociclib and ribociclib) in women with metastatic breast cancer.
Observational cross-sectional retrospective study. Inclusion criteria: patients who started treatment with palbociclib or ribociclib before December 2018.
The following variables were recorded: baseline characteristics (age, menopausal status, drug in combination, previous hormonal therapy, previous chemotherapy regimens, de novo metastatic disease and visceral metastases), hematological parameters (neutrophil and leukocyte count), liver function tests (transaminases and total bilirubin) and QT interval for ribociclib at the beginning of the first 3 cycles and after day 14 of cycles 1 and 2.
The number and cause of dose reductions (DR) and dose interruptions (DI) related to adverse events and relative dose intensity (RDI) for the first 3 cycles were analyzed.
Continuous variables are expressed as mean (standard deviation) or median (interquartile range).
Thirty-four patients were included (29 with palbociclib and 5 with ribociclib). The median age was 61.7 years (18.0 years) and 82.9% were postmenopausal women. The drug in combination was letrozole (n=18), fulvestrant (n=14), anastrozole (n=1) and exemestane (n=1). 85.3% of patients had received previous hormonal therapy and 73.5% previous chemotherapy regimens. 32.4% had de novo metastatic disease and 64.7% visceral metastases.
Neutropenia was observed in 96.5% of patients with palbociclib (17.2% grade 1, 51.7% grade 2 and 27.6% grade 3) and 100.0% with ribociclib (60.0% grade 2 and 40.0% grade 3). All patients presented leukopenia, for palbociclib 20.7% grade 1, 62.1% grade 2 and 17.2% grade 3 and for ribociclib 20.0% grade 1, 40.0% grade 2 and 40.0% grade 3. There were no moderate/severe elevations of transaminases, with a 27.6% grade 1 ALT elevation for palbociclib and 40.0% for ribociclib. No hyperbilirubinemia or QT prolongation for ribociclib were recorded.
Four patients with palbociclib (13.7%) and one with ribociclib (20.0%) required a DR; at least one DI was required for 13 patients with palbociclib (44.8%) and 4 with ribociclib (80.0%), associated with grade 2-3 neutropenia. The mean RDI was 92.3% (11.6%) for palbociclib vs 87.2% (17.0%) for ribociclib.
The hematological adverse events were very frequent in patients treated with palbociclib or ribociclib, with a high rate of neutropenia and leukopenia. These toxicities required numerous dose reductions and dose interruptions. The use of these drugs demands a strict control and monitoring.