The Experts below are selected from a list of 255 Experts worldwide ranked by ideXlab platform

Bruno Daniele - One of the best experts on this subject based on the ideXlab platform.

  • ramucirumab in elderly patients with hepatocellular carcinoma and Elevated alpha fetoprotein after sorafenib in reach and reach 2
    Liver International, 2020
    Co-Authors: Masatoshi Kudo, Peter R. Galle, Josep M Llovet, Richard S Finn, Arndt Vogel, Kenta Motomura, Eric Assenat, Philippe Merle, Giovanni Brandi, Bruno Daniele
    Abstract:

    BACKGROUND & AIMS: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with Alpha-Fetoprotein (AFP) ≥400 ng/mL showed an overall survival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥400 ng/mL by three prespecified age subgroups (<65, ≥65 to <75, ≥75 years). METHODS: Individual patient data were pooled from REACH (baseline AFP ≥400 ng/mL) and REACH-2. Kaplan-Meier and Cox proportional hazards regression methods (stratified by study) assessed OS, progression-free survival (PFS), time to progression (TTP), and patient-reported outcomes (Functional Hepatobiliary System Index-8 [FHSI-8] score). RESULTS: 542 patients (<65 years: n = 302; ≥65 to <75 years: n = 160; ≥75 years: n = 80) showed similar baseline characteristics between ramucirumab and placebo. Older subgroups had higher hepatitis C and steatohepatitis incidences, and lower AFP levels, than the <65 years subgroup. Ramucirumab prolonged OS in patients <65 years (hazard ratio [HR], 0.753; 95% CI 0.581-0.975), ≥65 to <75 years (0.602; 0.419-0.866), ≥75 years (0.709; 0.420-1.199), PFS and TTP irrespective of age. Ramucirumab showed similar overall safety profiles across subgroups, with a consistent median relative dose intensity ≥97.8%. A trend towards a delay in symptom deterioration in FHSI-8 with ramucirumab was observed in all subgroups. CONCLUSIONS: In this post-hoc analysis, ramucirumab showed a survival benefit across age subgroups with a tolerable safety profile, supporting its use in advanced HCC with Elevated AFP, irrespective of age, including ≥75 years.

  • Ramucirumab in elderly patients with hepatocellular carcinoma and Elevated Alpha-Fetoprotein after sorafenib in REACH and REACH-2.
    Liver International, 2020
    Co-Authors: Masatoshi Kudo, Peter R. Galle, Josep M Llovet, Richard S Finn, Arndt Vogel, Kenta Motomura, Eric Assenat, Philippe Merle, Giovanni Brandi, Bruno Daniele
    Abstract:

    BACKGROUND & AIMS: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with Alpha-Fetoprotein (AFP) ≥400 ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥ 400 ng/mL by three prespecified age subgroups (

Masatoshi Kudo - One of the best experts on this subject based on the ideXlab platform.

  • ramucirumab in elderly patients with hepatocellular carcinoma and Elevated alpha fetoprotein after sorafenib in reach and reach 2
    Liver International, 2020
    Co-Authors: Masatoshi Kudo, Peter R. Galle, Josep M Llovet, Richard S Finn, Arndt Vogel, Kenta Motomura, Eric Assenat, Philippe Merle, Giovanni Brandi, Bruno Daniele
    Abstract:

    BACKGROUND & AIMS: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with Alpha-Fetoprotein (AFP) ≥400 ng/mL showed an overall survival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥400 ng/mL by three prespecified age subgroups (<65, ≥65 to <75, ≥75 years). METHODS: Individual patient data were pooled from REACH (baseline AFP ≥400 ng/mL) and REACH-2. Kaplan-Meier and Cox proportional hazards regression methods (stratified by study) assessed OS, progression-free survival (PFS), time to progression (TTP), and patient-reported outcomes (Functional Hepatobiliary System Index-8 [FHSI-8] score). RESULTS: 542 patients (<65 years: n = 302; ≥65 to <75 years: n = 160; ≥75 years: n = 80) showed similar baseline characteristics between ramucirumab and placebo. Older subgroups had higher hepatitis C and steatohepatitis incidences, and lower AFP levels, than the <65 years subgroup. Ramucirumab prolonged OS in patients <65 years (hazard ratio [HR], 0.753; 95% CI 0.581-0.975), ≥65 to <75 years (0.602; 0.419-0.866), ≥75 years (0.709; 0.420-1.199), PFS and TTP irrespective of age. Ramucirumab showed similar overall safety profiles across subgroups, with a consistent median relative dose intensity ≥97.8%. A trend towards a delay in symptom deterioration in FHSI-8 with ramucirumab was observed in all subgroups. CONCLUSIONS: In this post-hoc analysis, ramucirumab showed a survival benefit across age subgroups with a tolerable safety profile, supporting its use in advanced HCC with Elevated AFP, irrespective of age, including ≥75 years.

  • Ramucirumab in elderly patients with hepatocellular carcinoma and Elevated Alpha-Fetoprotein after sorafenib in REACH and REACH-2.
    Liver International, 2020
    Co-Authors: Masatoshi Kudo, Peter R. Galle, Josep M Llovet, Richard S Finn, Arndt Vogel, Kenta Motomura, Eric Assenat, Philippe Merle, Giovanni Brandi, Bruno Daniele
    Abstract:

    BACKGROUND & AIMS: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with Alpha-Fetoprotein (AFP) ≥400 ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥ 400 ng/mL by three prespecified age subgroups (

Peter R. Galle - One of the best experts on this subject based on the ideXlab platform.

  • Ramucirumab in patients with advanced HCC and Elevated Alpha-Fetoprotein (AFP): Outcomes by treatment-emergent ascites.
    Journal of Clinical Oncology, 2020
    Co-Authors: Masafumi Ikeda, Peter R. Galle, Tatsuya Yamashita, Josep Llovet, Kun Liang, Chunxiao Wang, Sachi Sakaguchi, Paolo Abada, Ryan C Widau
    Abstract:

    4644 Background: REACH and REACH-2 investigated ramucirumab (RAM) vs placebo (PL) in patients (pts) with advanced HCC following sorafenib, with REACH-2 enrolling only pts with baseline AFP ≥400 ng/mL. Ascites is common in HCC and associated with poorer outcomes. An exploratory analysis of outcomes by treatment-emergent (TE)-ascites was done. Methods: Pts with HCC, Child-Pugh A, ECOG PS ≤1, prior sorafenib, and no clinically meaningful ascites were randomized (REACH 1:1; REACH-2 2:1) to RAM 8 mg/kg or PL Q2W. A pooled meta-analysis of independent pt data (stratified by study) from REACH-2 and REACH (AFP ≥400 mg/mL) was done. OS and PFS were evaluated by Kaplan-Meier estimator and Cox models. Prognosis of TE-ascites in OS was evaluated by multivariate Cox models (adjusted for baseline ECOG PS, AFP, macrovascular invasion (MVI), and treatment [trt]). Results: Baseline characteristics were generally balanced between TE-ascites and non-ascites pts; however, more pts with ascites had MVI at baseline. Any-grade ascites was reported at a higher rate in RAM than PL (66 [21%] vs 33 [15%] pts, respectively), with most being low grade. Rate of Gr ≥3 ascites was similar between arms (15 [5%] vs 9 [4%] pts). Median time to onset (43 vs 47 days) and median duration of ascites (13 vs 18 days) were similar in RAM vs PL, with furosemide (22%) and spironolactone (19%) as most common trt and paracentesis (18%) as most common procedure for ascites in both arms. Ascites trended as a prognostic factor for OS after adjustment (with vs without; HR=1.3, 95% CI: 0.99, 1.62). Ascites was more commonly linked with hypoalbuminemia (odds ratio 4.9, 95% CI: 2.5, 9.3), but was not associated with proteinuria or hypertension. TEAEs occurred more frequently in pts with ascites in both arms. The most frequent Gr ≥3 TEAE in pts with ascites was hypertension. One RAM pt discontinued trt due to ascites. RAM trt was beneficial irrespective of presence of ascites (Table), and pts with ascites received more post-discontinuation therapy on RAM than PL (18% vs 6%). Conclusions: Acknowledging limitations of sample size, RAM provided a survival benefit in pts who did or did not experience TE-ascites. RAM was well tolerated and no new safety findings were observed. Clinical trial information: NCT011400347; NCT02435433 . [Table: see text]

  • ramucirumab in elderly patients with hepatocellular carcinoma and Elevated alpha fetoprotein after sorafenib in reach and reach 2
    Liver International, 2020
    Co-Authors: Masatoshi Kudo, Peter R. Galle, Josep M Llovet, Richard S Finn, Arndt Vogel, Kenta Motomura, Eric Assenat, Philippe Merle, Giovanni Brandi, Bruno Daniele
    Abstract:

    BACKGROUND & AIMS: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with Alpha-Fetoprotein (AFP) ≥400 ng/mL showed an overall survival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥400 ng/mL by three prespecified age subgroups (<65, ≥65 to <75, ≥75 years). METHODS: Individual patient data were pooled from REACH (baseline AFP ≥400 ng/mL) and REACH-2. Kaplan-Meier and Cox proportional hazards regression methods (stratified by study) assessed OS, progression-free survival (PFS), time to progression (TTP), and patient-reported outcomes (Functional Hepatobiliary System Index-8 [FHSI-8] score). RESULTS: 542 patients (<65 years: n = 302; ≥65 to <75 years: n = 160; ≥75 years: n = 80) showed similar baseline characteristics between ramucirumab and placebo. Older subgroups had higher hepatitis C and steatohepatitis incidences, and lower AFP levels, than the <65 years subgroup. Ramucirumab prolonged OS in patients <65 years (hazard ratio [HR], 0.753; 95% CI 0.581-0.975), ≥65 to <75 years (0.602; 0.419-0.866), ≥75 years (0.709; 0.420-1.199), PFS and TTP irrespective of age. Ramucirumab showed similar overall safety profiles across subgroups, with a consistent median relative dose intensity ≥97.8%. A trend towards a delay in symptom deterioration in FHSI-8 with ramucirumab was observed in all subgroups. CONCLUSIONS: In this post-hoc analysis, ramucirumab showed a survival benefit across age subgroups with a tolerable safety profile, supporting its use in advanced HCC with Elevated AFP, irrespective of age, including ≥75 years.

  • Ramucirumab in elderly patients with hepatocellular carcinoma and Elevated Alpha-Fetoprotein after sorafenib in REACH and REACH-2.
    Liver International, 2020
    Co-Authors: Masatoshi Kudo, Peter R. Galle, Josep M Llovet, Richard S Finn, Arndt Vogel, Kenta Motomura, Eric Assenat, Philippe Merle, Giovanni Brandi, Bruno Daniele
    Abstract:

    BACKGROUND & AIMS: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with Alpha-Fetoprotein (AFP) ≥400 ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥ 400 ng/mL by three prespecified age subgroups (

Massimo Pandolfo - One of the best experts on this subject based on the ideXlab platform.

  • Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2
    Nature Genetics, 2004
    Co-Authors: Maria-céu Moreira, Sandra Klur, Mitsunori Watanabe, Andrea H Németh, José-carlos Moniz, Christine Tranchant, Patrick Aubourg, Meriem Tazir, Lüdger Schöls, Massimo Pandolfo
    Abstract:

    Ataxia-ocular apraxia 2 (AOA2) was recently identified as a new autosomal recessive ataxia. We have now identified causative mutations in 15 families, which allows us to clinically define this entity by onset between 10 and 22 years, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia and Elevated Alpha-Fetoprotein (AFP). Ten of the fifteen mutations cause premature termination of a large DEAxQ-box helicase, the human ortholog of yeast Sen1p, involved in RNA maturation and termination.

Philippe Merle - One of the best experts on this subject based on the ideXlab platform.

  • ramucirumab in elderly patients with hepatocellular carcinoma and Elevated alpha fetoprotein after sorafenib in reach and reach 2
    Liver International, 2020
    Co-Authors: Masatoshi Kudo, Peter R. Galle, Josep M Llovet, Richard S Finn, Arndt Vogel, Kenta Motomura, Eric Assenat, Philippe Merle, Giovanni Brandi, Bruno Daniele
    Abstract:

    BACKGROUND & AIMS: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with Alpha-Fetoprotein (AFP) ≥400 ng/mL showed an overall survival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥400 ng/mL by three prespecified age subgroups (<65, ≥65 to <75, ≥75 years). METHODS: Individual patient data were pooled from REACH (baseline AFP ≥400 ng/mL) and REACH-2. Kaplan-Meier and Cox proportional hazards regression methods (stratified by study) assessed OS, progression-free survival (PFS), time to progression (TTP), and patient-reported outcomes (Functional Hepatobiliary System Index-8 [FHSI-8] score). RESULTS: 542 patients (<65 years: n = 302; ≥65 to <75 years: n = 160; ≥75 years: n = 80) showed similar baseline characteristics between ramucirumab and placebo. Older subgroups had higher hepatitis C and steatohepatitis incidences, and lower AFP levels, than the <65 years subgroup. Ramucirumab prolonged OS in patients <65 years (hazard ratio [HR], 0.753; 95% CI 0.581-0.975), ≥65 to <75 years (0.602; 0.419-0.866), ≥75 years (0.709; 0.420-1.199), PFS and TTP irrespective of age. Ramucirumab showed similar overall safety profiles across subgroups, with a consistent median relative dose intensity ≥97.8%. A trend towards a delay in symptom deterioration in FHSI-8 with ramucirumab was observed in all subgroups. CONCLUSIONS: In this post-hoc analysis, ramucirumab showed a survival benefit across age subgroups with a tolerable safety profile, supporting its use in advanced HCC with Elevated AFP, irrespective of age, including ≥75 years.

  • Ramucirumab in elderly patients with hepatocellular carcinoma and Elevated Alpha-Fetoprotein after sorafenib in REACH and REACH-2.
    Liver International, 2020
    Co-Authors: Masatoshi Kudo, Peter R. Galle, Josep M Llovet, Richard S Finn, Arndt Vogel, Kenta Motomura, Eric Assenat, Philippe Merle, Giovanni Brandi, Bruno Daniele
    Abstract:

    BACKGROUND & AIMS: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with Alpha-Fetoprotein (AFP) ≥400 ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥ 400 ng/mL by three prespecified age subgroups (