Abstract PO1-04-10: Body Mass Index and Treatment Efficacy in advanced Luminal Breast Cancer: Insights from the GEICAM/2013-02 (PEARL) trial
Authors: Alva Manuel , López-Tarruella Sara , Zielinski Christoph , Ruíz - Borrego Manuel , Turner Nicholas , Ciruelos Eva , Muñoz Montserrat , Bermejo Begoña , Margelí Mireia , Antón Antonio , Kahan Zsuzsanna , Csöszi Tibor , Casas Maribel , Murillo Laura , Murillo Serafin Morales , Alba Emilio , Yam Einav Nili-Gal , Guerrero Angel , Calvo Lourdes , Haba-Rodríguez Juan de la , Ramos Manuel , Álvarez Isabel , García-Palomo Andrés , Koehler María , García-Sáenz José Ángel , Chacón J. Ignacio , Swift Claire , Thallinger Christiane , Gil-Gil Miguel , Martín Miguel 
Published: May 2024

Abstract
Background: Endocrine therapy (ET) and treatment directed against molecular targets (CDK 4/6, PI3K, mTOR) constitute the basis of initial treatments for patients with advanced luminal breast cancer. Most of these treatments are oral and have been developed at a fixed dose, without weight adjusted dosing. There is little evidence on the influence that patients’ weight might have on clinical outcomes of these oral drugs in the context of a randomized clinical trial. The present study analyzes the potential impact of the weight of patients treated in the two cohorts of the PEARL trial (NCT02028507) on Progression-Free Survival (PFS), Overall Survival (OS) and the incidence of side effects in each treatment arm.
Methods: GEICAM/2013-02 (PEARL) is a multicenter, phase III randomized clinical trial that enrolled patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) who progressed to a prior aromatase inhibitor. Patients were randomized 1:1 to receive ET + palbociclib or capecitabine. Patient weight was assessed based on baseline body mass index (BMI) categories: normal (BMI ≤25 Kg/m2), overweight (BMI 25-29.9 Kg/m2) and obesity (BMI ≥30 Kg/m2). Cox's stratified proportional hazard model was used for survival analysis. Adverse events were assessed and graded according to National Cancer Institute common terminology criteria for adverse events (NCI-CTCAE) version 4.0.
Results: A total of 600 patients were included in the study and all were evaluable for the weight-based analysis, including 301 in the ET +palbociclib arm and 299 in the capecitabine arm. The distribution of patient’s weights is shown in Table 1. For the Intention-to-treat (ITT) population, no significant difference in the median OS was found between the different weight categories (Normal: 32.8 months vs overweight: 31.9 months, [p=0.467]; obese: 32 months [p=0.407]).
Specifically, for patients with normal weight, the median PFS was 9.3 months in the ET + palbociclib group compared to 9.0 months in the capecitabine group (hazard ratio (HR) 0.83, 95% confidence interval [CI]: 0.61-1.13; p=0.23). In the overweight group, the PFS was 7.5 months in the ET+palbociclib group and 11.1 months in the capecitabine group (HR 1.17, 95% CI: 0.87-1.58; p=0.30) while for the obese group, the PFS was 5.7 months vs 11.7 months (HR 1.14, 95% CI: 0.82-1.59; p=0.43), respectively.
No substantial differences in the incidence of grade ≥ 3 events were observed when considering weight categories in the different treatment groups (capecitabine arm (Normal: 60%, Overweight: 70.4%, Obese: 61.6%) and ET+palbociclib arm (Normal: 74.5%, Overweight: 76.1%, Obese: 51.6%).
Conclusions: Our findings, despite not finding statistically significant differences, suggest a potentially clinically relevant trend towards improved PFS with capecitabine in overweight and obese patients compared to those receiving palbociclib plus ET. The impact of weight on the outcomes with fixed-dose oral drugs warrants further investigation in future studies.
Table 1.
Citation Format: Manuel Alva, Sara López-Tarruella, Christoph Zielinski, Manuel Ruíz - Borrego, Nicholas Turner, Eva Ciruelos, Montserrat Muñoz, Begoña Bermejo, Mireia Margelí, Antonio Antón, Zsuzsanna Kahan, Tibor Csöszi, Maribel Casas, Laura Murillo, Serafin Morales Murillo, Emilio Alba, Einav Nili-Gal Yam, Angel Guerrero, Lourdes Calvo, Juan de la Haba-Rodríguez, Manuel Ramos, Isabel Álvarez, Andrés García-Palomo, María Koehler, José Ángel García-Sáenz, J. Ignacio Chacón, Claire Swift, Christiane Thallinger, Miguel Gil-Gil, Miguel Martín. Body Mass Index and Treatment Efficacy in advanced Luminal Breast Cancer: Insights from the GEICAM/2013-02 (PEARL) trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-04-10.