Effect of prior treatment status on the efficacy and safety of ipilimumab monotherapy in treatment-naive and previously treated patients with advanced melanoma

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 9055-9055 ◽  
Author(s):  
J. A. Thompson ◽  
D. Berman ◽  
J. Siegal ◽  
D. Minor ◽  
A. Amin ◽  
...  
BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Giancarlo Comi ◽  
Mark S. Freedman ◽  
José E. Meca-Lallana ◽  
Patrick Vermersch ◽  
Byoung Joon Kim ◽  
...  

Abstract Background In this pooled, post hoc analysis of a phase 2 trial and the phase 3 TEMSO, TOWER, and TENERE clinical trials, long-term efficacy and safety of teriflunomide were assessed in subgroups of patients with relapsing multiple sclerosis (MS) defined by prior treatment status. Methods Patients were classified according to their prior treatment status in the core and core plus extension periods. In the core period, patients were grouped according to treatment status at the start of the study: treatment naive (no prior disease-modifying therapy [DMT] or DMT > 2 years prior to randomization), previously treated with another DMT (DMT > 6 to ≤24 months prior to randomization), and recently treated with another DMT (DMT ≤6 months prior to randomization). In the core plus extension period, patients were re-baselined to the time of starting teriflunomide 14 mg and grouped according to prior treatment status at that time point. Efficacy endpoints included annualized relapse rate (ARR), probability of confirmed disability worsening (CDW) over 12 weeks, and Expanded Disability Status Scale (EDSS) score. The incidence of adverse events was also assessed. Results Most frequently received prior DMTs at baseline were glatiramer acetate and interferon beta-1a across treatment groups. Teriflunomide 14 mg significantly reduced ARR versus placebo in the core period, regardless of prior treatment status. In the core and extension periods, adjusted ARRs were low (0.193–0.284) in patients treated with teriflunomide 14 mg across all subgroups. Probability of CDW by Year 4 was similar across subgroups; by Year 5, the percentage of patients with 12-week CDW was similar in treatment-naive patients and patients recently treated with another DMT (33.9 and 33.7%, respectively). EDSS scores were stable over time in all prior-treatment subgroups. There were no new or unexpected safety signals. Limitations include selective bias due to patient attrition, variability in subgroup size, and lack of magnetic resonance imaging outcomes. Conclusions The efficacy and safety of teriflunomide 14 mg was similar in all patients with relapsing MS, regardless of prior treatment history. Trial registration Phase 2 trial core: NCT01487096; Phase 2 trial extension: NCT00228163; TEMSO core: NCT00134563; TEMSO extension: NCT00803049; TOWER: NCT00751881; TENERE: NCT00883337.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8570-8570
Author(s):  
F. L. Locke ◽  
J. I. Clark ◽  
T. F. Gajewski

8570 Background: Although much focus has been placed on immunotherapy for melanoma, further development of chemotherapy approaches is needed. Melanoma is responsive to platinum compounds and taxanes, but there is limited experience with combinations of these agents. Oxaliplatin has been reported to have detectable activity in melanoma, and a phase I study has identified a tolerable dose and schedule of oxaliplatin in combination with docetaxel and hematopoietic growth factor support. GM-CSF has a theoretical advantage of immune potentiation. These considerations supported study of oxaliplatin, docetaxel, and GM-CSF in patients with advanced melanoma. Methods: Eligibility included intact organ function, PS=2, at most one prior chemotherapy and one prior immunotherapy, no prior treatment with oxaliplatin or taxanes, and no chremophor allergy. After premedication, docetaxel was administered day 1 at 85 mg/m2, then oxaliplatin on day 2 at 85 mg/m2. GM-CSF (5 μg/kg) was administered s.c. days 3–12. Cycles were 21 days in length, and disease reevaluation was performed every 2 cycles by RECIST criteria. Results: 20 patients were enrolled, 13 with 1 prior therapy, 5 with 2 prior therapies, and 2 previously untreated. Six patients did not complete 2 cycles and were not formally evaluable for response. One patient who failed 2 prior treatment regimens experienced a minor response and received 10 cycles of therapy, and 4 patients had stable disease. The rest showed PD after 2 cycles. Notable toxicities included 7 cases of grade III/IV neutropenia and 2 hypersensitivity reactions. Conclusions: This combination of oxaliplatin, docetaxel, and GM-CSF has limited clinical activity in previously treated patients with advanced melanoma. Exploration in treatment-naive patients may still be warranted. No significant financial relationships to disclose.


Haemophilia ◽  
2007 ◽  
Vol 13 (1) ◽  
pp. 9-11 ◽  
Author(s):  
L. NEMES ◽  
T. LISSITCHKOV ◽  
A. KLUKOWSKA ◽  
G. DOBACZEWSKI ◽  
V. KOMRSKA ◽  
...  

Author(s):  
Eileen Fonseca ◽  
David R Walker ◽  
Gregory P Hess

Background: Warfarin and dabigatran etexilate (DE) are oral anticoagulants (OAC) that reduce stroke risk among patients with nonvalvular atrial fibrillation (AF). However, DE does not require titration and INR monitoring. This study examined whether emergency department (ED) rate of admissions differed between the two therapies. Methods: Admission rate was evaluated for hospital encounters initiated in the ED, with a primary or secondary discharge diagnosis of AF between 1/1/2011-3/31/2012, with DE or warfarin administered during the encounter, and excluding encounters of valvular AF patients. Encounters were identified from a hospital Charge Detail Masters database containing 387 eligible hospitals. Samples were propensity score matched using nearest neighbor within a caliper of 0.20 standard deviations of the logit, without replacement, and a 2:1 match. Admission rates were estimated for encounters representing previously-treated patients and those representing treatment-naive patients using binominal generalized linear models, fitted by generalized estimating equations (clustered by hospital). Covariates estimating the propensity score and admission rate included age, payer type, use of bridging agents, AF as primary or secondary diagnosis, CHADS 2 and HAS-BLED scores, comorbid conditions, and hospital attributes. As a sensitivity analysis, admission rate was also estimated from the unmatched sample. Results: Matched samples included 2,688 warfarin and 1,344 DE ED encounters of previously-treated patients out of 15,053 and 1,367 ED encounters, respectively; and 2,578 warfarin and 1,289 DE ED encounters of OAC-treatment-naive patients out of 8,361 and 1,406 ED encounters, respectively. There were too few (n<5) matched encounters where the patient had prior OAC use but were new to the drug administered during the encounter, so these were excluded. No covariates used in matching had standardized mean differences > 10% after matching. Among the previously-treated sample, the estimated admission rate was 3.2% lower for DE compared to warfarin (88.3% vs. 91.5%, p=0.010) with sensitivity analysis confirming a lower admission rate for DE (91.1% vs. 93.8%, delta=2.7%, p=0.001). Among the treatment-naive sample, DE had a 1.2% lower admission rate compared to warfarin (95.2% vs. 96.3%, p=0.048). Sensitivity analysis confirmed a lower admission rate for DE (95.5% vs. 97.0%, delta=1.5%, p=0.001). Conclusions: While the vast majority of AF encounters initiated in the ED result in admission, encounters where patients were treated with DE as continuing or new therapy were less likely to be admitted compared to similar encounters where warfarin was administered.


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