Results of an exploratory analysis suggested that the progression-free survival (PFS) of patients with advanced/metastatic breast cancer treated with the CDK4/6 inhibitor abemaciclib was not influenced by body mass index (BMI). These findings were reported in the Journal of the National Cancer Institute.
Although being overweight/obese has been associated with worse clinical outcomes in women with estrogen receptor (ER)-positive, early-stage breast cancer, the impact of BMI on treatment outcomes in the setting of metastatic breast cancer has not been well investigated.
In this post-hoc analysis, data were pooled from 2 randomized, placebo-controlled phase 3 clinical trials (MONARCH-2 [ClinicalTrials.gov Identifier: NCT02107703] and MONARCH-3 [ClinicalTrials.gov Identifier: NCT02246621]) evaluating the risks and benefits of adding abemaciclib to either fulvestrant or an aromatase inhibitor in women with ER-positive, HER2-negative advanced or metastatic breast cancer.
The primary study endpoint of this analysis was PFS according to 2 BMI subgroups (ie, underweight/normal [25 kg/m2 or less] and overweight/obese [above 25 kg/m2]) in those receiving albemaciclib or placebo. Secondary endpoints included overall response rate (ORR) and safety.
Of the 1138 patients included in this analysis, 757 and 381 patients received abemaciclib and placebo, respectively, in addition to an endocrine therapy backbone. While very few patients were classified as underweight, approximately, 43%, 30%, and 25% had BMIs in the normal, overweight, and obese ranges, respectively.
A key study finding was that, for those patients receiving albemaciclib, there was no significant difference in median PFS for the subgroup with a BMI of less than 25 kg/m2 (22 months) compared with the subgroup characterized by a BMI greater than 25 kg/m2 (21.7 months; hazard ratio [HR], 1.03; 95% CI, 0.83 to 1.27; P =.81).
Similar findings were observed for the patients receiving placebo where median PFS was 10.8 months for those categorized as having an underweight/normal BMI compared with 12.7 months for those with a BMI considered to represent overweight or obesity (HR, 0.81; 95% CI, 0.64 to 1.04; P =.10).
Furthermore, similar analyses performed using the 4 BMI categories did not shown significant differences in PFS across BMI subgroups for those receiving either abemaciclib or placebo.
However, in the abemaciclib treatment group, ORR was significantly lower for those with a BMI of 25 kg/m2 or higher (41.6%) compared with less than 25 kg/m2 (49.4%; odds ratio [OR], 0.73; 95% CI, 0.54-0.99; P =.04). In contrast, for those receiving placebo, a higher ORR was observed for the overweight/obese BMI subgroup (30.7%) compared with the underweight/normal BMI subgroup (21.1%; OR, 1.65; 95% CI; 1.02-2.67; P =.04).
Regarding treatment-related adverse effects in patients treated with abemaciclib, the incidence of grade 3 or higher neutropenia was significant higher in those with a BMI of less than 25 kg/m2 (29.3%) compared with 25 kg/m2 or higher (21.7%; P =.02).
In their concluding remarks, the study authors noted that “adding abemaciclib to [endocrine therapy] prolongs PFS regardless of BMI, showing that overweight/obese patients also benefit from this regimen.”
However, they further noted that their results “elicit the possibility of a better effect of abemaciclib in normal/underweight patients compared to overweight/obese” while also commenting that “a future study integrating body composition parameters could more precisely analyze the impact of overweight and obesity in the outcomes of patients treated with abemaciclib plus [endocrine therapy].”
Franzoi MA, Eiger D, Ameve L, et al. Clinical implications of body mass index in metastatic breast cancer patients treated with abemaciclib and endocrine therapy. J Natl Cancer Inst. Published online August 3, 2020. doi:10.1093/jnci/djaa116