Over-all Population Research Articles

Achieving clinical outcomes with benralizumab in severe eosinophilic asthma patients in a real-world setting: ORBE II study

BackgroundThe ORBE II study aimed to describe the characteristics and clinical outcomes of adult patients with severe eosinophilic asthma (SEA) treated with benralizumab in a real-world setting in Spain.MethodsORBE II (NCT04648839) was an observational, retrospective cohort study in adult SEA patients who had been prescribed benralizumab. Demographic and clinical data of 204 SEA patients were collected 12 months prior to benralizumab initiation (baseline) and at follow-up. Exacerbation rate, asthma symptoms, maintenance oral corticosteroid (OCS) use and lung function were evaluated, among other variables.ResultsA total of 204 SEA patients were evaluated. Mean (standard deviation, SD) age of the study population was 56.4 (12.4) years, 62.3% were women and mean (SD) duration of asthma was 15.1 (12.7) years. Median (Q1–Q3) follow-up duration was 19.5 (14.2–24.2) months. At baseline, 72.6% of the overall population (OP) presented blood eosinophil counts ≥ 300 cells/µL; 36.8% had comorbid chronic rhinosinusitis with nasal polyps (CRSwNP); 84.8% reported at least one severe exacerbation, and 29.1% were OCS-dependent. At 1 year of follow-up, patients receiving benralizumab treatment had a 85.6% mean reduction in exacerbations from baseline, and 81.4% of patients achieved zero exacerbations. We also found a clinically relevant mean (SD) increase in pre-bronchodilator (BD) FEV1 of 331 (413) mL, with 66.7% of patients achieving a pre-BD FEV1 increase ≥ 100 mL, and 46.3% of patients achieving a pre-BD FEV1 ≥ 80% of predicted. Regarding symptom control, 73.8% of the OP obtained an ACT score ≥ 20 points. After 1 year of follow-up, mean reduction in the daily OCS dose was 70.5%, and complete OCS withdrawal was achieved by 52.8% of the OCS-dependent patients. Almost half (43.7%) of the OP on benralizumab met all four criteria for clinical remission. Patients with concomitant CRSwNP obtained similar or enhanced outcomes.ConclusionsThese data support the real-world benefits of benralizumab in SEA patients, and particularly in those with concomitant CRSwNP.Trial registrationNCT04648839.

Tislelizumab (TIS) versus sorafenib (SOR) in first-line (1L) treatment of unresectable hepatocellular carcinoma (HCC): The RATIONALE-301 European/North American (EU/NA) subgroup.

4082 Background: HCC is one of the most commonly diagnosed cancers globally. Most cases occur in Asia, although a number of patients (pts) are affected in Europe and North America. In the phase 3, open-label RATIONALE-301 trial (NCT03412773), TIS, a PD-1 inhibitor, showed non-inferior overall survival (OS) versus SOR (hazard ratio 0.85, 95% CI: 0.71, 1.02), and a favorable safety profile, in 1L treatment of pts with unresectable HCC. Here, efficacy and safety of TIS versus SOR in the RATIONALE-301 EU/NA subgroup were compared with the overall population (OP). Methods: Systemic therapy-naïve adults with histologically confirmed HCC were randomized (1:1) to receive TIS (200 mg IV Q3W) or SOR (400 mg orally BID) until disease progression, intolerable toxicity, or withdrawal. The primary endpoint was OS; secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and duration of response (DoR) by blinded independent review committee per RECIST v1.1, and safety. Results: In the EU/NA subgroup (172/674 pts randomized), at data cutoff (July 11, 2022), median (m) OS follow-up was 37.9 months (mo) (TIS) vs 38.5 mo (SOR). At baseline, fewer pts in the EU/NA subgroup had Barcelona Clinic Liver Cancer (BCLC) Stage C disease (70% vs 78%) and extrahepatic spread (51% vs 62%), and more had a non-viral etiology (60% vs 24%) or underlying HCV infection (28% vs 13%) than in the OP, respectively. Distribution of other baseline characteristics was generally similar between the EU/NA subgroup and the OP. Efficacy data in the EU/NA subgroup were consistent with the OP. Numerically longer mOS and mDoR, higher ORR, and similar mPFS were observed with TIS versus SOR in the EU/NA subgroup. In the EU/NA safety population, incidence of ≥grade 3 treatment-emergent adverse events (TEAEs; 46% vs 66%), ≥grade 3 treatment-related TEAEs (TRAEs; 17% vs 50%), and TRAEs leading to discontinuation (9% vs 15%) was lower with TIS versus SOR, respectively, similar to the OP. Conclusions: In the RATIONALE-301 EU/NA subgroup, mOS of TIS was non-inferior versus SOR, consistent with the findings from the OP. Numerically longer mOS and mDoR, and a higher ORR was seen with TIS versus SOR in the EU/NA subgroup, which had a higher rate of pts with non-viral etiology and a slightly lower number of pts with advanced-stage disease (BCLC Stage C) compared with the OP. Clinical trial information: NCT03412773 . [Table: see text]

Prognostic value of tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer (BC): A focus on inflammatory BC.

1098 Background: Circulating tumor cells (CTCs) are an independent prognostic factor in metastatic breast cancer (MBC). The prognostic value of CTCs and the optimal cutoff for patients (pts) with inflammatory breast cancer (IBC), one of the most aggressive types of BC, has not been fully established. Recent evidence showed the complementary prognostic value of tumor-derived extracellular vesicles (tdEVs) to CTCs in MBC. The significance of tdEVs in IBC is unexplored. This study aimed to assess the prognostic value of CTCs and tdEVs in metastatic IBC. Methods: This study retrospectively analyzed 308 pts with MBC enrolled at Northwestern University (Chicago, IL) before starting a new line of therapy between 2016 and 2021 (NU16B06 trial). Blood samples were processed for CTCs using the CellSearch system. We applied the open source ACCEPT software to archived CellSearch images to enumerate CTCs and tdEVs. TdEVs cutoff levels were <20 (low), 20-79 (intermediate), and ≥80 (high), as previously reported. The association of CTCs and tdEVs with overall survival (OS) was tested in the overall population (OvP) and IBC pts. Results: Of the 308 pts, 69 were diagnosed with IBC. 51% of pts received first-line therapy. CTCs enumerated by ACCEPT were strongly correlated with manual count (r=0.86) and hence used for this analysis. Median CTC count was 1 [interquartile range (IQR) 0-7] in IBC pts and 3 (IQR 0-14) in non-IBC (p=0.11). A significantly lower median tdEVs count was observed in IBC (7; IQR 3-45) than in non-IBC (22; IQR 4-137) pts (p=0.03). In IBC, higher CTC and tdEV counts were seen in the triple negative subtype (p=0.03) and non-visceral involvement (p=0.02), respectively. In the OvP median OS (mOS) was worse among pts with ≥5 CTCs (HR 2.6; p=0.001) and with elevated tdEVs (HR 3.3; p<0.001). Only tdEVs were independently associated with poorer OS in multivariable analysis. In pts with <5 CTCs there was a stepwise decrement in OS with increased tdEVs count (p=0.3); in pts with ≥5 CTCs, elevated tdEVs levels were associated with significantly worse OS (p=0.03). IBC pts with ≥5 CTCs had shorter mOS (8 vs 47 months; HR 3.6; p<0.001); this association was weaker using ≥1 as CTC cutoff (HR 2.4; p=0.01). OS was adversely associated with increasing tdEVs levels (33 vs 23 vs 7 months for low, intermediate, and high subgroups, respectively; HR 3.7; p=0.001). Furthermore, elevated tdEVs were associated with shorter mOS in pts with ≥1 (p=0.055) and ≥5 CTCs (p=0.6). Among pts with <5 CTCs no significant difference emerged among tdEVs subgroups (p=0.6). Conclusions: This study confirmed the strong prognostic significance of CTCs and tdEVs in MBC, including IBC. Pts with IBC had fewer CTCs and tdEVs compared to non-IBC, probably due to the predominant lymphatic spread of IBC. tdEVs offer the possibility to better define prognosis of IBC pts. Further studies are needed to evaluate their complementarity to CTCs.

Prognostic factors associated with malignant somatic transformation (MST) of germ cell tumors (GCT) in a Mexican cohort: The experience of the Instituto Nacional de Cancerología, Mexico (NCIM).

427 Background: MST is a rare entity defined as the development of somatic non-germ cell malignancies within GCT, its incidence varies between 2.7% and 8.6% of GCT’s. Previously reported favorable prognostic factors include synchronous diagnosis of MST and GCT, absence of non-pulmonary visceral metastases (NPVM) and presence of rhabdomyosarcoma. Methods: Retrospective study to describe prognostic factors of MST in GCT in a Hispanic population. Patients (pts) with diagnosis of MST from 2006 to 2019 were identified from the GCT database of the NCIM. Pts’ characteristics and outcomes were collected from clinical charts and recorded. Overall survival (OS) was performed with the Kaplan Meier (KM) method in the whole cohort and in patients with advanced disease (AD) (stage II and III). Comparisons were calculated with the log-rank test for KM and Chi squared test for categorical factors. Results: Seventy-one pts with MST were included in the overall population (OP). Non-seminoma 95.8%; testicular primary 97.2%; clinical stage (CS) I 32.4%, II 16.3%, III 49.3%; S2-S3 42.3%, 39.6% poor IGCCCG prognosis, 11.3% NPVM. Type of MST: 56.3% rhabdomyosarcoma (RMS), 21.1% spindle cell sarcoma, 12.7% PNET, 9.9% adenocarcinoma. 18.3% more than 1 MST histology. Median follow-up: 43.8 months (m). For the OP, mOS 71.1m (95% CI 80.0 – 119.2). OS for CS I have not been reached (NR). Forty-seven pts with AD were included, mOS 37m (95% CI 9.69 – 64.36). Characteristics associated with prognosis for OS for the OP and the AD cohorts are summarized in table. Pts with AD and RMS had more frequently a synchronous tumor (87.5% vs 58.3%, p=0.02) and absence of surgery for MST (70.8% vs 37.5%, p=.02). Conclusions: As far as we know, this is the largest cohort of hispanic pts with MST. Prognostic factors differed between OP and AD cohorts. Pts with MST and AD have a poor prognosis. Synchronous diagnosis of MST and presence of rhabdomyosarcoma are adverse prognostic factors for AD pts. Further study with a larger population is needed to verify these findings. Univariate analysis for OS.[Table: see text]

311 Effects of ruxolitinib cream in patients with atopic dermatitis with head and/or neck involvement

Atopic dermatitis (AD) often involves the head and/or neck (HN). In two phase 3 studies (TRuE-AD1, TRuE-AD2), 1249 patients (≥12 y) with AD for ≥2 y, an Investigator’s Global Assessment (IGA) score of 2/3, and 3%–20% affected body surface area were randomized (2:2:1) to twice-daily 0.75% or 1.5% ruxolitinib (RUX) cream (Janus kinase [JAK] 1/JAK2 inhibitor) or vehicle cream for 8 weeks of double-blind treatment. In this analysis, pooled efficacy at Week 8 was assessed by the proportion of patients achieving IGA treatment success (IGA of 0/1 and ≥2-grade improvement from baseline), ≥75% improvement in Eczema Area and Severity Index (EASI-75) vs baseline, and ≥4-point improvement in itch Numerical Rating Scale score (NRS4) in patients who had HN involvement at baseline (n=696 [55.7% of randomized patients]); data in the overall population (OP) were also included.

Cardiac arrests in sports events

Purpose of the study: Sudden cardiac arrest during sports is an extremely uncommon event that has a very strong social impact. We aim to study the basic epidemiological characteristics and outcome when life support is performed and compare to those in overall population (OP).

Effectiveness of an oral diabetes-specific supplement on nutritional status, metabolic control, quality or life, and functional status in elderly patients. A multicentre study

The purpose of this study was to assess nutritional status, quality of life (QoL) and function in malnourished or at risk for malnutrition community-dwelling (CD) and nursing home-dwelling (NHD) elderly patients with type 2 diabetes mellitus (DM2), receiving treatment with a diabetes-specific oral nutritional supplement (DSONS). A prospective, multicentre, observational study was conducted. A DSONS (high-calorie, high-protein, with slow-digestible carbohydrate and high monounsaturated fatty acid - MUFA-content - Glucerna® 1.5 Cal) had been prescribed the week before inclusion. The following assessments were undertaken at baseline (BL), at week 6 (V1) and at month 3 (FV): body mass index (BMI), glycosylated haemoglobin (HbA1c), nutritional status (Mini Nutritional Assessment - MNA), QoL (EQ-5D questionnaire), and functional status (Katz Index - KIof Independence in Activities of Daily Living). The data were reported in the overall population (OP) and in the CD and NHD groups. A total of 402 patients aged 80.8±8.5 years were evaluable (44.5% men), including 61.7% CD and 38.3% NHD. BMI (kg/m2) increased in the OP from 22.0±3.5at BL to 22.5±3.6at V1 (p<0.001) and 23.0±3.7at the FV (p<0.001). BMI also increased in the CD group (p<0.001) and in the NHD group (p<0.001). HbA1c decreased in the OP from 7.3±1.1% at BL to 7.2±1.0% at V1 and 7.0±0.9% at the FV (p<0.001), in both the CD (p<0.001) and the NHD groups (p=0.020). The mean overall MNA score increased in the OP from 13.1±4.8at BL to 17.0±4.7at V1 and 18.6±5.1at the FV (p<0.001). The mean overall MNA score also increased in the CD (p<0.001) and the NHD groups (p<0.001). The mean overall EQ-5D score improved in the OP from 46.0±18.0at BL to 54.8±17.5at V1 and 59.7±18.8at the FV (p<0.001). The mean overall EQ-5D score also improved in the CD (p<0.001) and the NHD groups (p<0.001). Gastrointestinal adverse events were seen in only 2% of patients. Treatment compliance was 94.4%. In this study, conducted in routine, multicentre, clinical settings, the treatment with the high-calorie, high-protein, with slow-digestible carbohydrate, and high MUFA content DSNOS - Glucerna® 1.5 Cal-, was associated with improvements in HbA1c, nutritional status, BMI and QoL following 6 weeks and 3 months of treatment in both institutionalised and non-institutionalised elderly patients with diabetes who were malnourished or at risk for malnutrition. A slight improvement in functional status was also observed at 12 weeks. As this is an observational effectiveness study, a randomized controlled trial would be necessary to establish a causal relationship between the DSNOS and the described events.

Efficacy, safety, and cost-effectiveness (CE) analysis of pegfilgrastim (P) and lenograstim (L) in patients (pts) with nonmetastatic breast cancer (nmBC) receiving myelosuppressive chemotherapy (mCT).

e19620 Background: Neutropenia (N) is common in pts who receive mCT. This retrospective study was conducted to determine efficacy, safety and cost of single injection of P (6 mg) compared with daily L (263 μg), in primary prophilaxis of N in pts affected by nmBC, who received mCT. Methods: 50 women (median age 54 years) underwent to median 6 (range 4–8) CT doses with antracyclines +/- taxanes. At every cycle, 28 pts received daily L (median 5 injections from day 5 to 9), while 22 pts received one dose of P on day 2. Absolute neutrophil count, incidence of G3/G4-N, bone pain (BP: Numerical Rate Scale &gt;7) and CE analysis were evaluated. Results: In overall population (OP) incidence of G3-N and G4-N was 25% and 68%, respectively in L vs 22.7% and 41%, respectively in P; two cases (7%) of febrile N (FN) occurred in pts treated with L and three cases (13.6%) of FN in P. In 19 pts treated with FEC100 (10 pts L vs 9 pts P) we observed 0% of G3-N and 30% of G4-N in L while 33% of G3-N and 44% of G4-N in P. 31 pts received TAC/AC+T (18 pts L vs 13 pts P) with G3-N and G4-N 38.8% and 66.6%, respectively in L vs 15.3% and 30.7%, respectively in P. 18.2% of pts, who received P, had BP vs 35.7% in L. Reduction of CT doses was observed in 35.7% in L vs 41% in P. In Italy the cost of 1 injection of P was about 1489,00 euro compared with about 655,00 euro for 5 injections of L. Conclusions: In our experience, 1 injection of P was more effective and expensive than 5 daily administration of L to control N in OP and in particular in TAC/AC+T, while in FEC100, L was satisfactory with good CE profile. No difference about incidence of NF. Safety of P and L were similar with a lower incidence of BP in P.

Incidence of chemotherapy (CT)-induced amenorrhea in premenopausal patients (pts) with breast cancer (BC) following adjuvant anthracycline (A), cyclophosphamide (C), and taxane (T).

e11039 Background: CT may induce amenorrhea or menopause to a variable extent. These side-effects may impair or impede fertility, cause sexual dysfunction, bone loss and menopausal symptoms in many women. We analyzed incidence of amenorrhea in premenopausal pts affected by BC treated with CT. Methods: In this retrospective study we evaluated the incidence of amenorrhea in 24 premenopausal BC pts (43 median age years) treated with adjuvant A + C +/- T based CT. Overall population (OP) had regular menstrual cycle and no pts began hormone therapy, at the same time. Results: 10 pts (42%) received only A + C, 6 pts (25%) received A + C + T, 8 pts (33%) received A + C and after T. In 22 pts (92%) amenorrhea appeared during CT; in particular, 9/10 pts (90%) treated with A + C , 5/6 pts (83%) with A + C + T and 8/8 pts (100%) with A + C and after T. In OP amenorrhea appeared during first three cycles of CT in 18 pts (82%) and particularly 7 pts (32%) after 1 cycle, 7 pts (32%) after 2 cycles, 4 pts (18%) after 3 cycles and 4 pts (18%) in subsequent doses. Amenorrhea occurred within the first two doses of treatment in 14/22 pts (64%); in 6/9 pts (66.7%) treated with A + C, in 4/5 pts (80%) with A + C + T and in 4/8 (50%) with A + C and after T. In 7 pts (32%), median age 40 years, at the end of CT reappeared menstrual cycle. Conclusions: In our small experience the incidence of amenorrhea during CT was extremely high and there are no differences between subgroups undergoing to CT with A + C alone or combined with T. In the group of pts in which T were given concomitant with A and C, amenorrhea occurred earlier than the other two groups. Menstrual cycle reappeared at the end of CT in younger pts.

Quality Adjusted Time without Symptoms or Toxicities (Q-TWiST) of Ixabepilone (Ixa) Plus Capecitabine (Cape) Versus Capecitabine for Metastatic Breast Cancer (MBC) Patients with Poor Prognostic Features (PPF).

Abstract Background: Data for this analysis is provided by pooled data from 2 randomized phase III trials (046 and 048) comparing Ixa + Cape versus cape alone in women with MBC refractory to or pretreated with anthracyclines (A) and taxanes (T). Pre-specified sub-group analyses (SGA) were undertaken in MBC patients with PPF including triple negative phenotype (TN), symptomatic KPS 70-80 (KPS), and post adjuvant rapid relapse (PARR, recurrence ≤ 12 months after adjuvant A and T). For each SGA, a clinically meaningful PFS increase was seen with Ixa + Cape (Table 1), consistent with the overall population (OP). A significant overall survival (OS) improvement was not observed in the OP. In the SGA, the OS results were as follows: TN (10.3 vs 9.0 months, p=0.1802c), PARR (15.1 vs 12.5 months, p=0.2081c) and KPS (12.3 vs 9.5 months, p=0.0015c). Across SGA, treatment related adverse events (AEs) were more common for Ixa + Cape, but similar to the OP. A Q-TWiST analysis was undertaken for each SGA to evaluate the trade off between toxicity and PFS.Methods: The area under the OS curves for each SGA was partitioned into 3 health states: 1) Toxicity (TOX) - time the subject spent prior to progression with grade 3/4 treatment toxicity, 2) TWiST - time spent without grade 3/4 AEs prior to progression, 3) Relapse (REL) - time from progression to death or end of follow-up. Utility weights (UW) between 0 and 1 were assigned to the TOX and REL health states with the base case analysis using 0.5 for TOX and REL. The TWiST UW was assumed to equal 1.0 as the most favorable health state achievable. The utility weighted sum of the mean health state durations was derived and treatment comparisons were made. Sensitivity analyses were performed varying the UW of the TOX and REL states between 0 and 1 and calculating the differences in the weighted sum for all combinations.Results: For each SGA, all UW combinations for REL and TOX were associated with greater observed quality adjusted survival (QAS) durations for Ixa + Cape compared to Cape. The base case showed improvements in mean QAS in favor of Ixa + Cape (Table 1), with differences ranging from 4.9 to 9.6 weeks and the PARR group deriving the largest benefit.Median PFS and Mean QAS in Pooled PPF MBC Sub-Groups* Median PFSa, monthsMean QASb, weeksaPatient Sub-GroupsIxa + CapeCapeHR (95% CI)P value cIxa + CapeCapeP value cTN(N = 191) 4.2(N = 208) 1.70.63 (0.52 -0.77)&amp;lt;0.0001(N = 213) 35.3(N = 230) 30.40.0031KPS(N = 268) 4.6(N = 257) 3.10.76 (0.64 - 0.90)0.0021(N = 314) 39.8(N = 292) 33.4&amp;lt;0.0001PARR(N = 123) 5.6(N = 111) 2.80.58 (0.45 - 0.76)&amp;lt; 0.0001(N = 149) 45.6(N = 144) 36.00.0007*Pooled data from trials 046 and 048 a PFS computed on all randomized 046 patients and 048 patients randomized to measurable disease stratum. b QAS computed on all randomized patients from both studies c Not adjusted for multiple comparisonsConclusions: This Q-TWIST analysis supports the positive benefit:risk of Ixa + Cap in MBC patients with poor prognostic features, previously treated with an A and T. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5051.

Evaluation of Prognostic Variables and Scoring Systems in Normal Karyotyped Myelodisplastic Patients

Myelodysplastic Syndrome (MDS) comprises a group of heterogeneous hematological disorders with variable risk of leukemic evolution (LE) and short survival (SV). According to French-American-British (FAB) classification, MDS are divided into five morphological entities and the World Health Organization reclassified them eliminating Refractory Anemia (RA) with Excess of Blast in transformation (RAEBt) and Chronic Myelomonocytic Leukemia (CMML), among other changes. Around 40–60% of patients shows normal karyotype at diagnosis and, despite this finding which is associated with good prognosis, some of them show poor outcome. The aim of this study was to evaluate different variables and prognostics scoring systems in an overall population (OP) of normal karyotyped MDS patients and in the reduced population (RP) after eliminating RAEBt and CMML subgroups. This retrospective study was performed in a population of 152 MDS patients with normal karyotype at diagnosis distributed according to FAB into 59% RA/RA with ringed sideroblast, 23% RA with excess of blasts, 5% RAEBt and 13% CMML. The OP's median age was 67 (20–89) years with a sex ratio (M/F) of 1.53. The median follow-up was 25.7 (1–266) months (m) and there were 31 (20%) events of LE and 65 (43%) related-MDS death during this period. The OP showed a median SV of 57 m and time to LE (25%) of 44 m vs. 63 and 124 m, respectively for the RP. Age, sex, percentage of bone marrow (BM) blast, hemoglobin (Hb) level, platelets count and number of cytopenias were significant predictive variables for prognosis in both populations (Kaplan-Meier and Long-Rank test, p<0.05). Despite all applied scoring systems allowed to difference groups of risk, patient distribution among them showed variations which were more evident in the Intermediate ones. Multivariate analysis (Cox proportional Hazard Model, p<0.05) established that age, Hb level and % BM blast were the most important predictors for SV. Therefore, a new scoring system was developed coding % BM blast 0 if <5, 0.5 if 5–9, 1 if 10–19 and 1.5 if ≥20, age 0 if ≤60 and 0.5 if >60 years, Hb level 0 if ≥10 and 0.5 if <10g/dL. Three groups of risk were defined: Low (0+0.5), Intermediate (1+1.5) and High (>1.5) with median SV of 131, 32 and 13 m for the OP vs. 131, 43 y 18 m for the RP, respectively. Additionally, confirmed that IPSS includes better variables for LE, determining 3 groups of risk: Low, Intermediate and High (Intermediate-2 + High) with time to LE (25%) of >130, 22 and 4 m for the OP vs. >130, 39 y 21 m for the RP, respectively. Results showed that SV and LE risk should be evaluated separately in patients with normal karyotype using different variables to predict each one, at least in MDS-FAB classified patients or in those that present less than 20% of BM blasts and monocite counts lower than 1000/μL. These results would be helpful to develop better risk-adapted therapeutic strategies for MDS patients with normal karyotype.