Search results for "Phase iii trial"
showing 10 items of 13 documents
Prognostic and predictive factors in patients treated with ramucirumab (RAM) with advanced hepatocellular carcinoma (aHCC) and elevated alpha-fetopro…
2021
4146 Background: Elevated AFP in patients with aHCC is a poor prognostic factor with distinct molecular features, including high vascular endothelial growth factor (VEGF) signalling and increased angiogenesis. RAM, a human IgG1 monoclonal antibody, VEGF receptor 2 (VEGFR2) inhibitor, demonstrated improved survival vs placebo among patients with elevated AFP in the REACH-2 trial and is accepted as a standard of care for management of aHCC. We analyzed prognostic factors in patients with AFP ≥400 ng/mL and predictors of clinical benefit to RAM in an individual participant data (IPD) meta-analysis of the REACH and REACH-2 Phase III trials. Methods: Patients with aHCC, Child-Pugh A, ECOG perfo…
Novel therapeutic options and drug targets in MS
2013
2012 witnessed important developments for multiple sclerosis, including successful phase III trials of novel oral therapeutics and identification of the potassium channel KIR4.1 as an autoimmune target. Additionally, the lung was highlighted as an important site for immune-cell programming, and the relevance of a TNF receptor variant was clarified.
Efficacy and safety of ramucirumab (RAM) for advanced hepatocellular carcinoma (HCC) with elevated alpha-fetoprotein (AFP) following first-line soraf…
2019
Abstract Background REACH (NCT01140347) and REACH-2 (NCT02435433) were two global, randomized, double-blind, placebo (PL)-controlled multicenter, phase 3 studies of RAM vs PL in patients with HCC after prior sorafenib. REACH-2 confirmed overall survival (OS) benefit of RAM for patients with baseline AFP ≥400ng/mL, consistent with results in a prespecified subgroup of patients in REACH with AFP ≥400ng/mL. Methods Post-hoc pooled analyses were performed to examine efficacy and safety in three age subgroups ( Results Both intention-to-treat populations were pooled (542 patients in total). Within each age subgroup, baseline characteristics between treatment arms were similar. Patients of Conclu…
Intermittent intensified high-dose intravenous interferon alpha 2b (IFNa2b) for adjuvant treatment of stage III malignant melanoma: Pooled analysis o…
2013
e20028 Background: Adjuvant high-dose interferon (HDI) treatment of patients (pts) with malignant melanoma (MM) consists of 4 weeks intravenous (IV) induction with 20 MU/m² interferon (IFN) alpha 2b followed by 11 months of 10 Mio IU/m² IFN subcutaneously (sc). It is unclear whether both parts of the regimen are mandatory for the efficacy of HDI treatment. The adjuvant phase III trials DeCOG MM-ADJ-5 and the Italian Melanoma Intergroup (IMI) trial evaluated intermittent IV HDI (iHDI) regimens as compared to standard HDI. In both trials, the experimental arm consisted of iHDI for 3 or 4 cycles, respectively. To gain more insight into the role of iHDI in the adjuvant setting we performed a p…
Gemcitabine, oxaliplatin, levofolinate, 5-fluorouracil, granulocyte-macrophage colony-stimulating factor, and interleukin-2 (GOLFIG) versus FOLFOX ch…
2013
The GOLFIG-2 phase III trial was designed to compare the immunobiological activity and antitumor efficacy of GOLFIG chemoimmunotherapy regimen with standard FOLFOX-4 chemotherapy in frontline treatment of metastatic colorectal cancer (mCRC) patients. This trial was conceived on the basis of previous evidence of antitumor and immunomodulating activity of the GOLFIG regimen in mCRC. GOLFIG-2 is a multicentric open/ label phase III trial (EUDRACT: 2005-003458-81). Chemo-naive mCRC patients were randomized in a 1:1 ratio to receive biweekly standard FOLFOX-4 or GOLFIG [gemcitabine (1000 mg/m 2, day 1); oxaliplatin (85 mg/m2, day 2); levofolinate (100 mg/m2, days 1-2), 5-fluorouracil (5-FU) (400…
Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, mu…
2013
Contains fulltext : 118365.pdf (Publisher’s version ) (Closed access) BACKGROUND: Until now, only imatinib and sunitinib have proven clinical benefit in patients with gastrointestinal stromal tumours (GIST), but almost all metastatic GIST eventually develop resistance to these agents, resulting in fatal disease progression. We aimed to assess efficacy and safety of regorafenib in patients with metastatic or unresectable GIST progressing after failure of at least imatinib and sunitinib. METHODS: We did this phase 3 trial at 57 hospitals in 17 countries. Patients with histologically confirmed, metastatic or unresectable GIST, with failure of at least previous imatinib and sunitinib were rando…
Sorafenib for the treatment of hepatocellular carcinoma
2018
SUMMARY The multikinase inhibitor sorafenib, which inhibits targets related to tumor cell proliferation and angiogenesis, was the first systemic agent to demonstrate a significant improvement in the overall survival for patients with advanced hepatocellular carcinoma (HCC) in two large randomized controlled Phase III trials. Together with its manageable safety profile (mainly diarrhea, hand–foot skin reaction and fatigue), sorafenib was approved for the treatment of patients with (unresectable) HCC in 2007. Since then, sorafenib has been established as the standard of care in Child–Pugh A patients with advanced HCC or in those ineligible for or after failure of locoregional therapies in th…
What can platinum offer yet in the treatment of PS2 NSCLC patients? A systematic review and meta-analysis
2015
Abstract: Background: Randomized phase III trials showed interesting, but conflicting results, regarding the treatment of NSCLC, PS2 population. This meta-analysis aims to review all randomized trials comparing platinum-based doublets and single-agents in NSCLC PS2 patients. Materials and methods: Data from all published randomized trials, comparing efficacy and safety of platinum-based doublets to single agents in untreated NSCLC, PS2 patients, were collected. Pooled ORs were calculated for the 1-year Survival-Rate (ly-SR), Overall Response Rate (ORR), and grade 3-4 (G3-4) hematologic toxicities. Results: Six eligible trials (741 patients) were selected. Pooled analysis showed a significan…
HCC therapies--lessons learned.
2014
The antiangiogenic multikinase inhibitor sorafenib was the first systemic agent to demonstrate a significant improvement in the overall survival of patients with advanced hepatocellular carcinoma (HCC), thereby introducing molecularly-targeted therapy in a therapeutic field of unmet needs. However, survival benefits for patients on sorafenib treatment are modest in clinical practice and advancing the field is far more challenging than initially anticipated. Molecular and clinical heterogeneity diminishes signals of potential activity in unselected populations, and underlying liver cirrhosis seals the fate of many novel targeted agents by causing relevant toxicity and mortality. The failure …
Outcomes of hepatocellular carcinoma patients treated with sorafenib: a meta-analysis of Phase III trials
2019
Aim: To benchmark overall survival (OS) and time to radiological progression (TTP) of patients enrolled in randomized controlled trials (RCTs) assessing sorafenib in advanced hepatocellular carcinoma using individual participant survival data, and to meta-analyze prognostic factors for OS and TTP. Methods: RCTs were identified through literature search until December 2018. Individual participant survival was reconstructed with an algorithm from published Kaplan–Meier curves. Results: Ten RCTs were included. Median OS was 10.0 months (95% CI: 9.6–10.5), and median TTP was 4.1 months (95% CI: 3.8–4.3). Multivariable analyses showed HCV positivity, absence of macrovascular invasion and extra-…