Aim: Investigate the safety, pharmacokinetics (PK) and efficacy of BTH1677/cetuximab, with and without irinotecan, in patients with metastatic colorectal cancer (mCRC). Patients & methods: Patients with recurrent or progressive mCRC were assigned to BTH1677/cetuximab/irinotecan (group 1; n = 10) or BTH1677/cetuximab (group 2; n = 22). Adverse events, PK parameters and tumor response were assessed. Results & conclusion: Adverse events were consistent with those expected of the backbone therapy of cetuximab/irinotecan (group 1) or cetuximab alone (group 2). The BTH1677 PK profiles were similar in the two groups. The overall response rates were 30.0% (group 1) and 22.7% (group 2); in KRAS wild-type subset analysis, rates were 42.9% and 45.5%, respectively. BTH1677 therapy was tolerable and warrants further evaluation for treatment of mCRC.
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6 CSL Behring, King of Prussia, PA. RATIONALE: Hereditary angioedema (HAE) due to C1-esterase inhibitor (C1-INH) deficiency is known to have a significant negative impact on patients' health-related quality of life (HRQoL). We evaluated the impact of long-term prophylaxis with subcutaneous C1-INH ([C1-INH (SC)] Haegarda Ò , CSL Behring) on HRQoL in HAE patients treated in an openlabel extension (OLE) of the pivotal phase III COMPACT trial.METHODS: In the OLE, patients with > _4 HAE attacks within a consecutive 2-month period (N5126) self-administered C1-INH (SC) 40 or 60 IU/kg twice weekly for up to 52 or 140 weeks (US only). HRQoL was self-assessed by patients at various points during the OLE using several instruments, including the European Quality of Life-5 Dimensions (EQ-5D) questionnaire, Hospital Anxiety and Depression Scale (HADS), and Work Productivity and Activity Impairment (WPAI) assessment. RESULTS: With C1-INH (SC) 60 IU/kg, significant improvements from baseline to the end-of-study visit were observed on the EQ-5D, HADS, and 3 of 4 WPAI domains. Clinically meaningful improvements versus baseline (mean [95% CI]) were observed on the Health State Value (0.07 [0.01, 0.12]) and Visual Analogue Scale (7.45 [3.29, 11.62]) of the EQ-5D. Improvements were also noted on the HADS Depression (-0.95 [-1.57, -0.34]) and Anxiety (-1.23 [-2.08, -0.38]) scales and WPAI domains of Presenteeism (-23.33 [-34.86, -11.81]), Work Productivity Loss (-26.68 [-39.92, -13.44]), and Activity Impairment (-16.14 [-26.36, -5.91]). CONCLUSIONS: Long-term prophylaxis with C1-INH (SC) leads to significant and clinically meaningful improvements in various HRQoL measures in patients with HAE. J ALLERGY CLIN IMMUNOL FEBRUARY 2019 AB38 Abstracts SATURDAY
RATIONALE: Hereditary angioedema (HAE) with normal C1 inhibitor (nlC1-INH) is a rare condition, with clinical features similar to those of HAE with C1-INH deficit. Hormones have a special role as triggering factor. There is no biomarker for diagnosis, requiring a compatible clinical and familial history and/or identification of associated mutation (Factor 12, Angiopoietin 1 and Plasminogen). METHODS: We evaluated 295 patients (242 F: 53 M) out of 101 families with confirmed diagnosis of HAE nlC1-INH from 16 reference centers in Brazil. RESULTS: 72.9% (215/295) were symptomatic (194F:21M) and 27.1% (80/295) asymptomatic with age range 3 -91 years (median: 36). Genetic evaluation showed: F12 mutation 178/245 (72.6%); angiopoietin1 in 4/245 and 63/245 had unknown mutation. Symptoms initiated between 2 -68 years old (median518). Main triggering factors: hormones 68.3%; stress 59.6%; trauma 47.6%; dental therapy 13.9%; unknown 13% and others 27%. Edema occurred in: face 84.6%; abdomen 75.5%; extremities 61.1%; laryngeal 36.1%; tongue 23.1% and others. Three patients died due to HAE. One third of the patients improved after contraceptive withdrawal only; 21.3% (36) treated on demand; continuous prophylaxis was used in 68.6% and 18.3% for surgical procedures; 22.5% increased doses of prophylactic medications during the attacks. Main prophylactic drug was tranexamic acid (n545). CONCLUSIONS: F12 mutation was present in a high number of our patients in comparison with other reports. Symptoms persisted in the majority of patients although estrogen therapy was interrupted. Plasmin inhibitor was effective in HAE nlC1-INH. RATIONALE: Prodromal symptoms (PS) in bradykinin-mediated angioedema (B) have been well described however data regarding prodromes in histamine-mediated angioedema (H) is lacking. We assessed the prevalence, types and reliability of prodromes in spontaneous histaminergic angioedema. METHODS: 73 patients (men and non-pregnant women between the ages of 18-70) receiving care at the US HAEA Angioedema Center were recruited for an anonymous 11 question survey. 30 patients had spontaneous histamine-mediated angioedema and 43 patients had either of the following bradykinin-mediated forms of angioedema: hereditary angioedema (HAE) with C1 inhibitor deficiency/dysfunction or HAE with normal C1 inhibitor. Frequencies were summarized and statistical analyses were calculated using Fisher's exact, Mann-Whitney U or Independent t-tests. RESULTS: 95.3% of B and 66.7% of H patients reported PS prior to their last angioedema (AE) attack (p50.002) and 97.6% of B and 80% of H patients reported PS associated with any previous AE attacks. The average number of PS before the last AE attack was 6.17 in B and 2.35 in H (p<0.005). The most frequent PS in B was upset stomach/nausea (63.4%) and in H was cutaneous numbness/tingling (40%). 71% of B and 63% of H patients reported being able to predict AE attacks based on PS at least 75% of the time. PS were followed by AE attacks at least 75% of the time in 80.5% of B and 45% of H patie...
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