Background: Our prior analysis of the MONARCH2/3 trials showed no difference in progression-free survival rates according to BMI in patients treated with abemaciclib and endocrine therapy for hormone receptor-positive, HER2-negative advanced breast cancer (Franzoi et al, JNCI 2021). However, a statistically inferior overall response rate with abemaciclib and endocrine therapy was observed in patients with BMI ≥25. In the present study, we examined the impact of baseline BMI on mean KI67% changes, achievement of complete cell cycle arrest (CCCA) and clinical and radiological responses in patients included in the phase II NEOMONARCH trial, which randomized patients to receive a 2-week initial treatment with either abemaciclib, letrozole, or abemaciclib and letrozole followed by 14 weeks of the combination of abemaciclib and letrozole as neoadjuvant therapy for hormone receptor-positive, HER2-negative early-stage breast cancer patients. Patients and methods: This is an exploratory, individual patient-level, post-hoc analysis of the NEOMONARCH study. Data was assessed through a research proposal submission in the Vivli platform. Patients were classified according to baseline BMI into underweight/normal weight (BMI <25 kg/m2) and overweight/obese (BMI≥25 kg/m2). The primary endpoint was the percent change in Ki67 expression from baseline to 2 weeks of treatment. The analysis was performed using the Fisher exact test for categorical variables and the Wilcoxon rank-sum test and its multisample generalization (Kruskal-Wallis test) for continuous variables. CCCA was analyzed as per the main study definition: patients with Ki67 % ≤2.7 after 2 weeks of treatment. Results were considered significant if p-value <0.05. Results: Out of 263 patients included in NEOMONARCH, A total of 222 patients (84.4%) had BMI information available, of whom 6 (2.7%) were underweight, 75 (33.8%) had normal weight, 77 (34.7%) were overweight and 64 (28.8%) were obese. Regarding baseline characteristics, patients with BMI ≥25 were predominantly Caucasian (p=0.001) and presented more with other histologies of breast cancer (p=0.007). There was no significant difference regarding baseline tumor grade or size, node status, ER/PR status, age, and Ki67% value at baseline according to BMI. In the overall cohort, mean Ki67% changes at 2 weeks were similar between the two BMI groups: - 19 (IQR -27.8 to -10.4) for patients with BMI <25 and -17.2 (IQR -26.8 to -11) for patients with BMI ≥25 (p=0.760). The proportion of patients achieving CCCA after 2 weeks of treatment was numerically higher for patients with BMI <25 vs ≥25 (56% vs 43%, respectively; p=0.096). Mean Ki67% reduction at 2 weeks was significantly higher for patients receiving the combination of abemaciclib + letrozole when compared to letrozole alone or abemaciclib alone, regardless of BMI. There was also no significant difference regarding radiological response (p=0.366) or clinical response (p=0.261) according to BMI at the end of the treatment period (16 weeks). Conclusions: In this exploratory analysis, BMI categorized by the threshold of 25 did not significantly impact KI67% changes or the proportion of patients achieving CCA after the initial 2 weeks of neoadjuvant therapy with abemaciclib, letrozole, or their combination. Moreover, BMI did not have an impact on radiological and clinical response rates after 14 weeks of treatment with letrozole and abemaciclib. Although limited by the small sample size, these results are reassuring that the combination of letrozole and abemaciclib appears to be active in the early setting regardless of baseline BMI.

Citation Format: Maria Alice Franzoi, Matteo Lambertini, Marcello Ceppi, Marco Bruzonne, Evandro de Azambuja. Implications of body mass index (BMI) on the biological and clinical effects of endocrine therapy and abemaciclib in the neoadjuvant setting [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-07.