BMI inversely associated with palbociclib-induced neutropenia

An inverse relationship may exist between BMI and palbociclib-induced neutropenia, according to study results presented at Miami Breast Cancer Conference.

“Providers may take extra caution when it comes to palbociclib-induced neutropenia by pre-emptively starting patients with lower BMI on lower doses of palbociclib,” Joseph C. Chang, PharmD, outpatient pharmacy manager at Kaiser Permanente in Los Angeles, and colleagues wrote. “[A] larger cohort is needed to elucidate the correlation between BMI and palbociclib-induced neutropenia. BMI or weight-based dosing should be explored in the future studies.”

Palbociclib (Ibrance, Pfizer) is the first cyclin dependent kinase 4/6 inhibitor to receive FDA approval.

The agent often is administered with hormonal therapy for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Results of the PALOMA-2 trial showed the combination of palbociclib and letrozole extended median PFS compared with placebo-letrozole (24.8 months vs. 14.5 months).

However, neutropenia is common among palbociclib-treated patients.

In PALOMA-2, two-thirds (66.4%) of those who received palbociclib-letrozole experienced grade 3 or grade 4 neutropenia, compared with 1.4% of those who received placebo-letrozole.

Asian patients in PALOMA-2 demonstrated a 10-fold greater risk for palbociclib-induced neutropenia than those of other races. However, it remained unclear whether an association existed between BMI and neutropenia.

Chang and colleagues conducted a retrospective cohort study to investigate PALOMA-2 findings in a real-life setting, aiming to identify potential associations between race, BMI and neutropenia. They also quantified hospitalization rates and ED visits among patients with palbociclib-induced neutropenia.

The analysis included 362 women aged 18 years or older treated at a Kaiser Permanente facility from 2015 through 2018.

Investigators obtained data on age, race, BMI and absolute neutrophil count during the first five treatment cycles via chart review.

Patients with no absolute neutrophil count results from the first five cycles of treatment and those who completed only one cycle of palbociclib were excluded.

The recommended palbociclib dose is 125 mg daily for 21 days, followed by 7 days off. Providers started some patients on 100-mg or 75-mg doses due to medical history or other factors.

Slightly less than half (44.2%; n = 160) of patients experienced grade 3 or grade 4 neutropenia; of these patients, 35 (22%) either were on a decreased dose or started on a 75-mg dose. Of the 30 patients whose dose was reduced to 75 mg, 15 (50%) developed grade 3 or grade 4 neutropenia.

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Average BMI at initiation of palbociclib treatment was significantly higher among patients who did not develop neutropenia than those who did experience the condition (29.78 kg/m² vs. 26.84 kg/m²; P < .001).

Results showed the percentage of patients with BMI of 18.5 kg/m² to 24.99 kg/m² was higher in the neutropenia group than the no-neutropenia group (40% vs. 30%). The percentage of patients with BMI of 25 kg/m² to 29.99 kg/m² was lower in the neutropenia group than the non-neutropenia group (42% vs. 56%).

Researchers observed no significant difference in neutropenia rates between Asian and non-Asian patients (56.4% vs. 42.7%). However, mean BMI of Asian patients who developed neutropenia was 23.86 kg/m², whereas mean BMI of Asian patients who did not develop neutropenia was 27.3 kg/m² (P = .025).

“Although Asian patients experienced grade 3 or [grade] 4 neutropenia significantly more often than [patients of] other races, no difference in the rates of neutropenia between Asian and non-Asian patients was observed,” Chang and colleagues wrote. “Hence BMI, rather than race, may be related to palbociclib-induced neutropenia.” – by Mark Leiser

Reference:

Chang JC, et al. Abstract 713. Presented at: Miami Breast Cancer Conference; March 7-10, 2019; Miami.

Disclosure: The authors report no relevant financial disclosures.