Clinical Implications of Body Mass Index in Metastatic Breast Cancer Patients Treated With Abemaciclib and Endocrine Therapy

Abstract

Background There are limited data regarding the impact of body mass index (BMI) on outcomes in advanced breast cancer, especially in patients treated with endocrine therapy (ET) + cyclin-dependent kinase 4/6 inhibitors. Methods A pooled analysis of individual patient-level data from MONARCH 2 and 3 trials was performed. Patients were classified according to baseline BMI into underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (≥30 kg/m2) and divided into 2 treatment groups: abemaciclib + ET vs placebo + ET. The primary endpoint was progression-free survival (PFS) according to BMI in each treatment group. Secondary endpoints were response rate, adverse events according to BMI, and loss of weight (≥5% from baseline) during treatment. Results This analysis included 1138 patients (757 received abemaciclib + ET and 381 placebo + ET). There was no difference in PFS between BMI categories in either group, although normal-weight patients presented a numerically higher benefit with abemaciclib + ET (Pinteraction = .07). Normal and/or underweight patients presented higher overall response rate in the abemaciclib + ET group compared with overweight and/or obese patients (49.4% vs 41.6%, odds ratio = 0.73, 95% confidence interval = 0.54 to 0.99) as well as higher neutropenia frequency (51.0% vs 40.4%, P = .004). Weight loss was more frequent in the abemaciclib + ET group (odds ratio = 3.23, 95% confidence interval = 2.09 to 5.01). Conclusions Adding abemaciclib to ET prolongs PFS regardless of BMI, showing that overweight or obese patients also benefit from this regimen. Our results elicit the possibility of a better effect of abemaciclib in normal and/or underweight patients compared with overweight and/or obese patients. More studies analyzing body composition parameters in patients under treatment with cyclin-dependent kinase 4/6 inhibitors may further clarify this hypothesis.

The obesity paradox in early and advanced HER2 positive breast cancer: pooled analysis of clinical trial data

“…Nonetheless, our study, which uses a much larger pooled clinical trial cohort, demonstrated contrasting results of pretreatment overweight/obese BMI being independently associated with improved survival outcomes in HER2 positive ABC. The cause of the difference between our study and Krasniqi et al 26 as well as between other ABC studies indicating a paradox 30,32 , that there is no BMI association 30,31,34,35 , or that high BMI is associated with poor outcomes [26][27][28][29] remains unknown; however, it does highlight the need for further investigation. In strength to the study herein the obesity paradox demonstrated was consistently observed across the four pooled HER2 positive ABC clinical trials (Supplementary Table 6).…”

“…Association between BMI and survival outcomes in HER2 positive ABC Data was available for 3496 HER2 positive ABC patients, of which 35 months [34][35][36] in MARIANNE, 47 months [46][47][48][49] in EMILIA, and 35 months [34][35][36] 2). Supplementary Table 5 outlines univariable analysis describing the association between BMI category and survival outcomes.…”

“…Where the BMI-survival relationship has been explored in advanced BC (ABC), the sample has generally been small (i.e., n < 800) and observational [26][27][28][29][30][31][32][33][34] . Further to this, most studies have been nonspecific regarding early versus ABC, ABC subtypes (e.g., HER2 positive disease), and/or treatments used [26][27][28][29][30][31][32][33][34][35] . Coincidingly, results have been conflicting with respect to whether a paradox exists in ABC 30,32 , some studies showing no association with BMI 30,31,34,35 , and others finding that higher BMI is associated with poorer outcomes [26][27][28][29] .…”

“…Further to this, most studies have been nonspecific regarding early versus ABC, ABC subtypes (e.g., HER2 positive disease), and/or treatments used [26][27][28][29][30][31][32][33][34][35] . Coincidingly, results have been conflicting with respect to whether a paradox exists in ABC 30,32 , some studies showing no association with BMI 30,31,34,35 , and others finding that higher BMI is associated with poorer outcomes [26][27][28][29] . Owing to these conflicts 26,[30][31][32] , as well as the known heterogeneity in the association between BMI and survival according to BC subtypes and treatment in EBC 6 , there is a need to establish the relationship between BMI and survival in HER2 positive ABC and HER2 positive EBC in patients receiving contemporary treatment options.…”

CDK4/6 Inhibitor Treatments in Patients with Hormone Receptor Positive, Her2 Negative Advanced Breast Cancer: Potential Molecular Mechanisms, Clinical Implications and Future Perspectives

“…Furthermore, body composition parameters may influence the prognosis in patients receiving CDK4/6 inhibitors. In a retrospective study, baseline sarcopenia (skeletal muscle index <40) was retrospectively associated with a significantly worse PFS, whereas a high visceral fat index and higher visceral fat density were associated with better PFS [ 64 ].…”