PSY6 THE ICATIBANT OUTCOME SURVEY:A PROSPECTIVE STUDY OF SAFETY AND EFFECTIVENESS OF ICATIBANT IN A ‘REAL WORLD' SETTING IN PATIENTS WITH HEREDITARY ANGIOEDEMA

Abstract Introduction: Treatment of MDS has undergone a dramatic change in recent years with the emergence of demethylating agents; however, there are limited data on the impact of these agents on OS in the "real-world" setting. The aim of this study is to evaluate the use and outcomes of different therapies in patients (pts) with International Prognostic Scoring System (IPSS)-defined Intermediate-2- and High-risk (higher-risk) MDS. Methods: The ERASME study (CEL-SMD-2012-01) is an observational, prospective study of pts with either MDS or chronic myelomonocytic leukemia (CMML); pts were defined using the 2008 World Health Organization (WHO) classification system. Initial pt management strategy was classified into 3 groups: active therapy (AT), such as chemotherapy or treatment with azacitidine (AZA), lenalidomide (LEN), etc.; allogeneic hematopoietic cell transplantation (HCT), which included those pts receiving other therapies before transplantation; and observation and support (OB&SP), which included red blood cell and platelet transfusions, and growth factors. OS rates of higher-risk pts are presented using the Kaplan-Meier method. Results: A total of 160 pts with higher-risk MDS were recruited between Jan 2013 and Feb 2015. Median follow-up was 8.6 months (interquartile range [IQR] 4.0-11.8). Pt characteristics are described in the Table. AT was the first therapeutic decision in 83 (52%) pts, HCT in 43 (27%), and OB&SP in 34 (21%). Within the AT group, 75 (90%) pts received AZA alone, 5 (6%) AZA plus chemotherapy, and 3 (4%) received other options; most pts (n = 78; 94%) were treated with a 7-day regimen. Among the 43 potential HCT candidates, 40 (93%) had received prior therapy: 25 (58%) with AZA alone, 8 (19%) with chemotherapy, 6 (14%) with AZA plus chemotherapy, and 1 (2%) with LEN; 3 (7%) had not received prior therapy. Of the potential HCT candidates, 20 had undergone transplantation within a median of 8 months (IQR 4.1-13.3); 7 (16%) pts died before transplantation and 16 (37%) are still awaiting transplantation. The main reasons for OB&SP being the initial pt strategy were disease risk (100%), age (95%), comorbidities (60%), and symptomatology (44%). At last follow-up, 70 of 160 pts (44%) had died after a median of 6 months (IQR 2.9-11.8): 34 (41%), 14 (32%), and 22 (65%) pts undergoing AT, HCT, and OB&SP, respectively (log-rank 6.9; P = 0.032). Median OS in pts who received AT, HCT, and OB&SP was 18.60 months (95% confidence interval [CI] 13.1-21.8), 14.92 months (95% CI 11.6-not reached), and 8.44 months (95% CI 4.3-13.4), respectively. Median OS was significantly longer in the AT group compared with the OB&SP group (hazard ratio [HR] 1.9; 95% CI 1.1-3.3; P = 0.0197). No statistically significant difference was observed in OS between pts treated with AT and those considered potential HCT candidates (HR 0.9; 95% CI 0.5-17.7; P = 0.8). Conclusions: The preliminary data from this observational, prospective study indicate that AT significantly prolongs OS compared with OB&SP when treating pts with higher-risk MDS in a real-world setting. AZA was the most common treatment in the AT group. Abstract presented on behalf of the ERASME Study Investigators Group. Table. Baseline characteristics of the MDS population (N = 160) Characteristic Age, median (IQR), years 73 (64.5-79.0) Male, n (%) 86 (53.8) Bone marrow blast count, median (IQR), % 12 (7.5-16.3) Hemoglobin level, median (IQR), g/dL 9.55 (8.0-10.6) Platelet count, median (IQR), × 109/L 64.75 (41.0-121.0) ANC, median (IQR), × 109/L 1 (0.47-2.20) Cytogenetic risk (by IPSS-R), n (%) Low 64 (40.0) Intermediate 9 (5.6) High 27 (16.9) Very High 39 (24.4) Missing data 21 (13.1) WHO classification, n (%) RCMD 17 (10.6) RAEB type 1 28 (17.5) RAEB type 2 94 (58.8) Unclassified 2 (1.3) Missing 1 (0.6) AML 20-30% blasts 18 (11.3) IPSS risk classification, n (%) Intermediate-2 86 (53.8) High 71 (44.4) Missing 3 (1.9) IPSS-R risk classification, n (%) Very Low 4 (2.5) Low 28 (17.5) Intermediate 20 (12.5) High 40 (25.0) Very High 46 (28.8) Missing 22 (13.8) AML, acute myeloid leukemia; ANC, absolute neutrophil count; FAB, French-American-British; IPSS-R, Revised-IPSS; RAEB, refractory anemia with excess blasts; RCMD, refractory anemia with multilineage dysplasia. Disclosures Off Label Use: Azacitidine was used to treat patients who are potential hematopoietic stem cell transplant candidates. Ramos:GlaxoSmithKline: Honoraria; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria; Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria. Rafel:Celgene Corporation: Employment. Valcárcel:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

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Safety and efficacy of nivolumab in metastatic renal cell carcinoma (mRCC): Final analysis from the NIVOREN GETUG AFU 26 study.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.542 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 542-542 ◽

Cited By ~ 7

Author(s):

Laurence Albiges ◽

Sylvie Negrier ◽

Cécile Dalban ◽

Christine Chevreau ◽

Gwenaelle Gravis ◽

...

Keyword(s):

Prospective Study ◽

Real World ◽

Kinase Inhibitors ◽

Objective Response ◽

Final Analysis ◽

Primary Objective ◽

Duration Of Treatment ◽

Safety And Efficacy ◽

Real World Setting ◽

Grade 3

542 Background: NIVOREN GETUG AFU 26 study, is a French multicenter prospective study to evaluate safety and efficacy of Nivolumab (N) in a broad “real world setting” in mRCC after failure of 1 or 2 tyrosine kinase inhibitors. Methods: Between February 2016 and June 2017, 729 pts have been enrolled across 27 institutions. Primary objective of the trial was safety assessed by grade ≥ 3 treatment related adverse event (TRAE). Results: Overall, 720 patients treated with N were included in this final analysis. All pts had clear cell mRCC. Median age was 64 years old, 77.4% were male, 84.7% had prior nephrectomy. ECOG PS was >1 in 15.0%, 21.3% pts had received prior everolimus, 22.4% pts had received more than 2 previous lines, IMDC risk groups were 18.3%/56.2%/25.5% for good/intermediate and poor risk respectively. Brain Metastasis at screening was noted in 83 (12.3%) pts. With a median follow up of 20.9 months (mo), median duration of treatment was 5.2 mo (0.5; 28.1) with 15% of pts still on therapy. Median PFS was 3.2 IC 95% [2.9; 4.6] mo. At the time of this analysis, 316 pts have died and 12 mo OS rate was 69% IC 95% [66; 73]. Objective response rate was 20.8% (1.2% CR, 19.6%PR). Stable disease was seen in 31.6% and PD in 47.6%. Noteworthy, 46.1% of pts were treated beyond progression. Overall, 123 pts (17.1%) have presented at least one grade ≥ 3 TRAE, including asthenia (2.4%), metabolic disorders (2.1%), gastro-intestinal disorders (1 .9%), musculoskeletal (1.7%), renal disorders (1.3%), hematologic (1.3%). 6 patients have developed grade 5 toxicity (2 cardiac failure, 1 macrophage activation syndrom, 1 Cerebral hemorrhage, 1 unknown). Treatment discontinuation due to any grade TRAE occurred in 54 pts (7.5%). Interestingly, pts with grade ≥ 3 TRAE had longer PFS than pts without grade ≥ 3 TRAE (HR 0.69 [0.55-0.87]). Conclusions: We report the primary objective analysis of the largest prospective real world setting study of N in mRCC. NIVOREN study demonstrates that N safety and efficacy in a “real world” prospective study are similar to the pivotal study. Grade ≥ 3 TRAE was associated with longer PFS. Clinical trial information: NCT03013335.

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Sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes in North India: A 12-month prospective study in real-world setting

International Journal of Clinical Practice ◽

10.1111/ijcp.13237 ◽

2018 ◽

Vol 72 (9) ◽

pp. e13237 ◽

Cited By ~ 4

Author(s):

Amerta Ghosh ◽

Ritesh Gupta ◽

Padam Singh ◽

Abhinav Dutta ◽

Anoop Misra

Keyword(s):

Type 2 Diabetes ◽

Prospective Study ◽

Real World ◽

North India ◽

Real World Setting ◽

Sodium Glucose Cotransporter

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Treatment of hereditary angioedema with icatibant: Efficacy in clinical trials versus effectiveness in the real-world setting

Allergy and Asthma Proceedings ◽

10.2500/aap.2014.35.3780 ◽

2014 ◽

Vol 35 (5) ◽

pp. 377-381 ◽

Cited By ~ 13

Author(s):

Marcus Maurer ◽

Hilary J. Longhurst ◽

Vincent Fabien ◽

H. Henry Li ◽

William R. Lumry

Keyword(s):

Clinical Trials ◽

Real World ◽

Hereditary Angioedema ◽

The Real ◽

Real World Setting

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Safety and efficacy of nivolumab in metastatic renal cell carcinoma (mRCC): Results from the NIVOREN GETUG-AFU 26 study.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.577 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 577-577 ◽

Cited By ~ 12

Author(s):

Laurence Albiges ◽

Sylvie Negrier ◽

Cécile Dalban ◽

Gwenaelle Gravis ◽

Christine Chevreau ◽

...

Keyword(s):

Prospective Study ◽

Real World ◽

Kinase Inhibitors ◽

Clear Cell ◽

Univariate Analysis ◽

Primary Objective ◽

Duration Of Treatment ◽

Safety And Efficacy ◽

Real World Setting ◽

Ecog Ps

577 Background: Nivolumab (N) has been approved for the treatment of mRCC after failure of 1 or 2 tyrosine kinase inhibitors (TKI) based on the results of Checkmate 025 study. Right after approval, we initiated the NIVOREN GETUG-AFU 26 study (NCT03013335), a French multicenter prospective study to evaluate safety and efficacy of N in a “real world setting”. Methods: Patients (pts) with clear cell mRCC could be enrolled if they had received at least one TKI. Compared with the pivotal trial, inclusion criteria allowed patients with more than 2 previous lines of treatment, including previous mTOR inhibitors, ECOG PS 2, asymptomatic brain metastases (BM) or impaired renal function. The primary objective of the study was the safety of N, efficacy being the main secondary objective. Between February 2016 and June 2017, 729 pts have been enrolled. We report the results from the first 528 pts. Results: All pts had clear cell mRCC, median age was 64, 77.2% were male. ECOG PS was > 1 in 73 pts (14.7%), 27.5% pts had received prior everolimus, 29.7% pts had received more than 2 previous lines, IMDC risk groups were 19%/54.9%/26.1% for good/intermediate and poor risk respectively; 69 (14%) pts had BM at screening. With a median follow up of 13.1 months, median duration of treatment was 4.1 months [0-15.6], with 31.4% of pts still on therapy. Treatment discontinuation due to adverse event (AE) occurred in (48) 13.3% pts . 64 serious related AE have been reported in 52 pts (9.9%) including 7 renal failures and 6 pneumonitis. Median PFS was 4.4 months 95%CI[3;4.6] . At the time of this analysis, 170 pts have died and 12 months OS rate was 66.4% 95%CI[ 61.7; 70.7]. In subgroups analysis, ECOG-PS > 1 (Hazard Ratio (HR) = 2.450 [1.704;3.523]), more than 2 previous lines (HR = 1.442 [1.059;1.963]) and prior use of everolimus (HR = 1.704 [1.250;2.322]) were associated with reduced OS in univariate analysis. Conclusions: We report the first analysis of the largest prospective real world setting study of N in mRCC. NIVOREN study demonstrates that N safety and efficacy in a “real world” prospective study are comparable to the pivotal study. Clinical trial information: NCT03013335.

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