Dataset Information

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.

SUBMITTER: Franzoi MA

PROVIDER: S-EPMC8023855 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCyclin-dependent kinases (CDK) 4 and 6 regulate G1 to S cell cycle progression and are often altered in cancers. Abemaciclib is a selective inhibitor of CDK4 and CDK6 approved for administration on a continuous dosing schedule as monotherapy or as combination therapy with an aromatase inhibitor or fulvestrant in patients with advanced or metastatic breast cancer. This Phase 1b study evaluated the safety and tolerability, pharmacokinetics, and antitumor activity of abemaciclib in combination with endocrine therapy for metastatic breast cancer (MBC), including aromatase inhibitors (letrozole, anastrozole, or exemestane) or tamoxifen.Patients and methodsWomen ≥18 years old with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) MBC were eligible for enrollment. Eligibility included measurable disease or non-measurable but evaluable bone disease by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, Eastern Cooperative Oncology Group performance status 0-1, and no prior chemotherapy for metastatic disease. Adverse events were graded by the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 and tumor response were assessed by RECIST v1.1.ResultsSixty-seven patients were enrolled and received abemaciclib 200 mg every 12 hours in combination with letrozole (Part A, n=20), anastrozole (Part B, n=16), tamoxifen (Part C, n=16), or exemestane (Part D, n=15). The most common treatment-emergent adverse events (TEAE) were diarrhea, fatigue, nausea, and abdominal pain. Grade 4 TEAEs were reported in five patients (one each with hyperglycemia, hypertension, neutropenia, procedural hemorrhage, and sepsis). There was no effect of abemaciclib or endocrine therapy on the pharmacokinetics of any combination study drug. Across all treated patients, the median progression-free survival was 25.4 months (95% confidence interval: 18.0, 35.8). The objective response rate was 38.9% in 36 patients with measurable disease.ConclusionsAbemaciclib in combination with multiple endocrine therapy options exhibited manageable safety and promising antitumor activity in patients with HR+, HER2- MBC.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT02057133.