Rivera, Ragene

Abstract Disclosure: E. Tama: None. R. Rivera: None. S. Fansa: None. D. Anazco: None. W. Ghusn: None. S. Faubion: None. A. Acosta: Consulting Fee; Self; Amgen Inc. Grant Recipient; Self; Vivus USA, Novo Nordisk. C. Shufelt: None. M.D. Hurtado: None. Introduction: Midlife women (ages 40 to 65) experience age-related weight gain (0.4-0.7 kg/year) due to physiologic and psychosocial changes. Evidence supports that age-related decrease in lean mass and its subsequent effect on energy expenditure are key physiologic factors. To date, the are no data describing if changes in the main regulators of energy intake (i.e., hunger, satiation, and satiety) across women’s lifespan play a role in weight gain during midlife. The aim of this study is to characterize measurements of satiation, satiety, and appetite sensations through early adulthood and midlife in women with obesity. Methods: This is a cross sectional study of women aged 19-65 with overweight or obesity who have undergone measurements of (i) body composition by DXA scan; (ii) resting energy expenditure (REE) by indirect calorimetry; (iii) satiation by calories consumed to satiation (CTS) during an ad libitum meal test; (iv) satiety by time needed to empty 50% of the stomach content (GEt1/2) in a gastric emptying study and plasma satiety hormone levels (PYY, GLP-1, and CCK); and (v) appetite sensations by visual analog scales (VAS) for hunger and fullness. We present data as mean ± standard deviation. We performed simple correlations between these variables and age. We performed multiple regression analyses to adjust for body composition and REE. Results: Our cohort included 552 mostly white (93%) women, with a mean age of 41±11 years and a mean BMI of 37±7 kg/m2. Increased age significantly correlated with higher waist circumference (r=0.1, p=0.006), waist/hip ratio (r=0.1, p=0.01), and total fat mass % (r=0.1, p=0.04); and with lower lean mass % (r=-0.1, p=0.04) and REE (r=-0.3, p<0.0001). Increased age was associated with decreased hunger sensation (i.e., lower preprandial VAShunger after an overnight fast, r=-0.1, p=0.04; and lower postprandial VAShunger 4hr after a standardized 320-kcal breakfast, r=-0.1, p=0.001), stronger satiation (i.e., lower CTS, r=-0.1, p=0.001), and more prolonged satiety (i.e., higher GEt1/2, r=0.1, p=0.02; higher postprandial GLP-1 levels, r=0.1, p=0.03; and higher postprandial VASfullness after and ad libitum meal, p=0.1, p=0.008). After adjusting for lean mass % and REE, the correlations between age and hunger sensations and satiation measurement, but not satiety measurements, were maintained. Conclusion: Our results show that older women have lower lean mass % and REE. After adjusting for these variables, older women experience decreased hunger sensation and achieve satiation with a lower number of calories. As these changes in theory would protect against midlife weight gain, the differences in body composition and REE remain the most likely culprit. Further research is necessary to investigate if there are other key factors that may contribute to weight gain such as the hedonic or emotional components of food intake. Presentation: 6/2/2024

Abstract Background: Three prior Phase III trials (E2100, AVADO, and RIBBON-1) established the clinical benefit of adding bevacizumab (BV) to various chemotherapies (chemos) as first-line treatment for metastatic breast cancer (MBC). A previous Phase III study (AVF2119g) in patients with predominantly heavily pre-treated MBC, in which BV was added to capecitabine (Cape), resulted in a significant increase in objective response rate (ORR), but did not meet the primary endpoint for progression-free survival (PFS). The current study, RIBBON-2, was designed to evaluate the efficacy and safety of the addition of BV to chemotherapies used as second-line treatment for MBC.Methods: Patients were randomized in a 2:1 ratio to chemo+BV or chemo+placebo (PL). Key eligibility criteria included one prior cytotoxic treatment for MBC, ECOG performance status of 0 to 1, and HER2-negative or unknown status. Prior to randomization, investigators chose one of the following chemo agents: taxane (T; paclitaxel 90 mg/m2/wk for 3 of the 4 weeks; paclitaxel 175 mg/m2, nab-paclitaxel 260 mg/m2, docetaxel 75–100 mg/m2, all given q3wk), gemcitabine (G; 1250 mg/m2 on Days 1 and 8 q3wk), Cape (2000 mg/m2 Days 1–14 q3wk), or vinorelbine (V; 30 mg/m2/wk). BV or PL was administered at 10 mg/kg q2wk or 15 mg/kg q3wk, depending on the chemo regimen. The primary endpoint of the study was investigator-assessed PFS pooled across the chemo cohorts. Key secondary endpoints included overall survival (OS), PFS within individual chemo cohorts, ORR, and safety.Results: 684 patients (T, 304; G, 160; Cape, 144; and V, 76) at 211 sites in 19 countries were randomized between February 2006 and June 2008. Overall, the two study arms were balanced for patient characteristics at baseline. The study met its primary endpoint of PFS pooled across chemo cohorts and also demonstrated a 10% increase in ORR when BV was added to chemo. At the interim analysis for OS, the median durations were 18 mo for chemo+BV and 16.4 mo for chemo+PL (see table).Across all chemo cohorts the incidence of BV-related AEs was consistent with data from previous studies. Hypertension was the only BV-related AE consistently increased in the chemo+BV arm across all chemo cohorts.Conclusions: The addition of BV to chemotherapies used for second-line treatment of MBC led to a significant improvement in PFS. The AE profile of BV in the overall study population and across the chemotherapy cohorts was consistent with that previously observed. Additional analyses, including PFS for the individual chemo cohorts, will be presented. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 42.