Abstract P1-14-06: Everolimus effect on hematologic parameters in a phase II clinical trial for metastatic estrogen receptor (ER) positive breast cancer
Authors: Chen A , Chen L , Romond E , Kadamyan V , Stevens M , Chambers M , Massarweh S 
Published: August 2014

Abstract
Background: Everolimus (RAD001) is increasingly used in combination with endocrine therapy for treatment of metastatic ER-positive breast cancer. Its beneficial effect notwithstanding, familiarity with its associated toxicities is critical for the treating oncologist. Here we present hematologic changes on everolimus from a phase II trial using a combination of everolimus and fulvestrant in metastatic ER-positive breast cancer after aromatase inhibitor failure (NCT00570921).
Methods: Complete Blood Counts (CBCs) were collected at baseline, 2 weeks, 4 weeks, and every 4 weeks thereafter while on treatment, as well as one month after discontinuation. Adverse events (AEs) were defined on protocol using Common Toxicity Criteria (CTC) version 3. Linear mixed modeling with random intercepts and slopes were used to study trends of studied parameters during treatment and comparisons were conducted using paired t-test. All p-values were two sided.
Results: There were 31 evaluable patients on trial. Anemia was reported in 22 patients (71%), thrombocytopenia in 17 (55%), and leukopenia in 14 (45%). All toxicities were grade 1 or 2 except for one grade 3 anemia deemed unrelated to study drug. To further analyze the observed changes and trends, we next studied red blood cell indices, including mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC), as well as differential white blood cell percent distribution. Both MCV and MCH decreased significantly over time (p&lt;0.0001) starting as early as the first 2 weeks of therapy. Not unexpectedly, there was no significant change observed in MCHC (p = 0.104). Interestingly, both MCV and MCH increased one month after discontinuation of treatment (p values &lt;0.0001 and 0.0003, respectively). Using the same linear mixed model, lymphocyte percentage decreased significantly over time while on therapy (p = 0.0408) but with no significant increase one month after discontinuation (p = 0.1476). There were no significant changes observed in either monocyte or neutrophil percentage.
Conclusion: Anemia, leukopenia, and thrombocytopenia are commonly observed on everolimus, albeit predominantly mild in nature. Changes in red blood cell indices start very early after treatment and appear readily reversible upon discontinuation, suggesting that these changes may not solely be due to suppression of hematopoiesis. The etiology for these changes is currently unclear. While leukopenia is relatively common, lymphopenia in particular is consistently observed and does not appear to be readily reversible in the first month after treatment discontinuation. This may be related to the risk of infection encountered while on everolimus. Regular monitoring and familiarity with the spectrum of CBC changes observed on everolimus is prudent with its increased use.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-14-06.