SAT0461 SHORT-TERM MONITORING OF DENOSUMAB EFFECT IN BREAST CANCER PATIENTS RECEIVING AROMATASE INHIBITORS USING REMS TECHNOLOGY ON LUMBAR SPINE

Background:Aromatase inhibitor (AI) therapy in women with estrogen receptor-positive (ER+) breast cancer (BC) causes accelerated bone loss and increased risk of osteoporosis and fractures as side effects. Denosumab (i.e. 60 mg twice a year) is a viable therapy against bone resorption, but the short-term monitoring of bone mineral density (BMD) change with time is still an unmet clinical need, since the current techniques (including dual-energy X-ray absorptiometry, DXA) require 1-2 years between two consecutive measurements [1]. Radiofrequency Echographic Multi Spectrometry (REMS), with high performance in terms of precision and repeatability [2], might be used in this setting of patients for short-term monitoring of bone health-related parameters.Objectives:The objective is the short-term monitoring of the effect of AIs with/without denosumab on bone health in BC patients using REMS and DXA scans at lumbar spine.Methods:Post-menopausal ER+ BC patients treated with adjuvant AIs were recruited. Two subgroups were identified, whether receiving also 60 mg of denosumab therapy every 6 months or not (named Group A and Group B, respectively). All patients underwent baseline DXA and REMS lumbar spine scans at time T0, previous to the first AI therapy, and after 12 months (time T1). REMS scan only was repeated also at 18 months (T2), since a 6-month interval between two consecutive scans is not recommended for DXA. The bone mineral density (BMD) was measured with both techniques.Results:Overall, 254 ER+ BC patients were enrolled (127 per group). The effect of denosumab on BMD is reported in Table. The BMD values obtained by DXA and REMS were not significantly different at T0 and T1, whereas the difference between Group A and B at T1 was statistically significant (p<0.001) both for REMS and DXA. At T2, REMS confirmed the increasing trend of BMD for Group A and the decreasing one for Group B, and the difference between groups was statistically significant (p<0.001). For each time point and each group, there were not statistically significant differences between DXA and REMS.Conclusion:Several studies have shown the effect of denosumab on BMD over a period not less than 2 years from the start of treatment. This study showed the feasibility of short-term follow-up using REMS lumbar spine scans at 6-month time steps.References:[1]Diez-Perez A et al, Aging Clin Exp Res 2019;31(10):1375–89[2]Di Paola M et al, Osteoporos Int 2018;30:391–402Table 1.BMD values, expressed as g/cm2, measured by DXA and REMS for Group A (patients receiving AIs only) and Group B (patients receiving AIs and denosumab) at baseline (T0), 12 months (T1) and 18 months (T2) from the start of therapy. Results are presented as median values with 25thand 75thpercentiles. P-values are obtained with a Mann-Whitney test.DXAREMSScan timeGroup AGroup BpGroup AGroup BpT00.840 (0.719-0.959)0.867 (0.723-0.958)0.990.833 (0.708-0.949)0.855 (0.714-0.973)0.77T10.823 (0.702-0.944)0.889 (0.749-0.990)0.0030.819 (0.691-0.927)0.887 (0.740-1.018)<0.001T2---0.801 (0.679-0.909)0.899 (0.754-1.020)<0.001Note:The authorsD. Ciardo, M. Ciccarese, F. Conversano, M. Di Paola, R. Forcignanò, A. Grimaldi, F.A. Lombardi, M. Muratore and P. Pisaniare listed in alphabetical orderDisclosure of Interests:None declare

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

DENOSUMAB FOR BONE METASTASES IN ADVANCED CANCER: CLINICAL EXPERIENCE AND SAFETY DATA ACCORDING TO TUMOUR TYPES

Background. Bone metastases are a common event in breast cancer and other tumours, such as prostate and lung cancer. The occurrence of SRE is frequent in presence of bone metastases. The impact of SRE on the quality of life is well established in all tumour types. The use of denosumab, a molecular target drug thatinhibits osteoclast activation, has changed the management of bone metastases in advanced cancer. Methods. Data of 81 pts with bone metastases from breast, prostate and lung cancer, treated in the last year with denosumab, were collected from three Institutions. The occurrence of SRE and safety of denosumab were evaluated in patients that cross from bisphosphonate to denosumab and in pts treated with denosumab upfront. Results. Breast cancer was 70% (N = 57), prostate 16% (N = 13), lung 14% (N = 11). Median age was 69 (34-86), median time from diagnosis to metastasis was 30 months (0-231), bone metastatic sites <3 in 43% pts, = 3 in 57% pts, 51% had extrabone disease. Previous treatment with bisphosphonate was in 38% pts (N = 31), 94% breast (N = 29) and 6% prostate (N = 2), respectively (“cross-over population”). Median time of bisphosphonate treatment was overall 31 months (2-114), 33 mos in breast (2-114), 6 mos in prostate (5.8-6.2). SRE before treatment with denosumab occurred in 54% pts: 80% breast, 7% prostate, 13% lung, respectively. SRE during treatment with denosumab was seen in 5% pts; 50% breast, 25% prostate, 25% lung, respectively. Hypocalcemia was seen in 10% overall: 63% breast, 25% prostate, 12% lung; median time of hypocalcemia was 24 days for all types of tumours. All patients had oral supplementation with calcium as prevention of hypocalcemia. ONJ was seen in 1% of the population. Bone disease progression was seen in 11% pts (56% breast, 22% prostate, 22% lung). Conclusion. Use of denosumab results safe in a population of patients with bone metastases and previous use of bisphosphonate, independently of tumour type; the occurrence of hypocalcemia is easily manageable with a fast recovery; nevertheless, supplementation with calcium is strongly recommended

Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists

Vitamin K antagonist (VKA) therapy for stroke prevention in atrial fibrillation (AF) requires monitoring of the international normalized ratio (INR). We evaluated the agreement between two INR audit parameters, frequency in range (FIR) and proportion of time in the therapeutic range (TTR), using data from a global population of patients with newly diagnosed non-valvular AF, the Global Anticoagulant Registry in the FIELD\u2013Atrial Fibrillation (GARFIELD-AF). Among 17\ua0168 patients with 1-year follow-up data available at the time of the analysis, 8445 received VKA therapy (\ub1antiplatelet therapy) at enrolment, and of these patients, 5066 with 653 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70\ua0905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56\ub70% vs 49\ub78%; median, 59\ub77% vs 50\ub70%). Although patient-level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0\ub7860 [0\ub7852\u20130\ub7867]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0\ub7829 [0\ub7821\u20130\ub7837]). The difference between FIR and TTR explained 17\ub74% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably