Author
Gerold Meinhardt
Other affiliations: Bayer Corporation, Schering AG
Bio: Gerold Meinhardt is an academic researcher from Bayer HealthCare Pharmaceuticals. The author has contributed to research in topics: Sorafenib & Regorafenib. The author has an hindex of 21, co-authored 61 publications receiving 5771 citations. Previous affiliations of Gerold Meinhardt include Bayer Corporation & Schering AG.
Papers
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University of Barcelona1, University of Bologna2, Taipei Veterans General Hospital3, Chiba University4, Pierre-and-Marie-Curie University5, University of Cambridge6, Tianjin Medical University7, University of Lorraine8, Kindai University9, National Taiwan University10, Icahn School of Medicine at Mount Sinai11, Catalan Institution for Research and Advanced Studies12, University of California, Los Angeles13, Bayer Corporation14, Bayer15, Bayer HealthCare Pharmaceuticals16, Fourth Military Medical University17
TL;DR: Regorafenib is the only systemic treatment shown to provide survival benefit in HCC patients progressing on sorafenIB treatment, and future trials should explore combinations of regorAFenib with other systemic agents and third-line treatments for patients who fail or who do not tolerate the sequence of sorafanib and regorafinib.
2,543 citations
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University of Barcelona1, Nihon University2, Taipei Veterans General Hospital3, Kindai University4, Peking Union Medical College5, Queen Mary University of London6, Kyungpook National University7, Asan Medical Center8, Tianjin Medical University9, Lenox Hill Hospital10, University of Bologna11, University of Tokyo12, Bayer HealthCare Pharmaceuticals13, Mount Sinai Hospital14
TL;DR: The data indicate that sorafenib is not an effective intervention in the adjuvant setting for hepatocellular carcinoma following resection or ablation.
Abstract: Summary Background There is no standard of care for adjuvant therapy for patients with hepatocellular carcinoma. This trial was designed to assess the efficacy and safety of sorafenib versus placebo as adjuvant therapy in patients with hepatocellular carcinoma after surgical resection or local ablation. Methods We undertook this phase 3, double-blind, placebo-controlled study of patients with hepatocellular carcinoma with a complete radiological response after surgical resection (n=900) or local ablation (n=214) in 202 sites (hospitals and research centres) in 28 countries. Patients were randomly assigned (1:1) to receive 400 mg oral sorafenib or placebo twice a day, for a maximum of 4 years, according to a block randomisation scheme (block size of four) using an interactive voice-response system. Patients were stratified by curative treatment, geography, Child-Pugh status, and recurrence risk. The primary outcome was recurrence-free survival assessed after database cut-off on Nov 29, 2013. We analysed efficacy in the intention-to-treat population and safety in randomly assigned patients receiving at least one study dose. The final analysis is reported. This study is registered with ClinicalTrials.gov, number NCT00692770. Findings We screened 1602 patients between Aug 15, 2008, and Nov 17, 2010, and randomly assigned 1114 patients. Of 556 patients in the sorafenib group, 553 (>99%) received the study treatment and 471 (85%) terminated treatment. Of 558 patients in the placebo group, 554 (99%) received the study treatment and 447 (80%) terminated treatment. Median duration of treatment and mean daily dose were 12·5 months (IQR 2·6–35·8) and 577 mg per day (SD 212·8) for sorafenib, compared with 22·2 months (8·1–38·8) and 778·0 mg per day (79·8) for placebo. Dose modification was reported for 497 (89%) of 559 patients in the sorafenib group and 206 (38%) of 548 patients in the placebo group. At final analysis, 464 recurrence-free survival events had occurred (270 in the placebo group and 194 in the sorafenib group). Median follow-up for recurrence-free survival was 8·5 months (IQR 2·9–19·5) in the sorafenib group and 8·4 months (2·9–19·8) in the placebo group. We noted no difference in median recurrence-free survival between the two groups (33·3 months in the sorafenib group vs 33·7 months in the placebo group; hazard ratio [HR] 0·940; 95% CI 0·780–1·134; one-sided p=0·26). The most common grade 3 or 4 adverse events were hand-foot skin reaction (154 [28%] of 559 patients in the sorafenib group vs four [ vs five [ Interpretation Our data indicate that sorafenib is not an effective intervention in the adjuvant setting for hepatocellular carcinoma following resection or ablation. Funding Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals.
721 citations
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University of Miami1, Icahn School of Medicine at Mount Sinai2, Fourth Military Medical University3, Kyungpook National University Hospital4, University of Verona5, Samsung Medical Center6, Yonsei University7, Taipei Veterans General Hospital8, University of Pittsburgh9, University of Alcalá10, Bayer HealthCare Pharmaceuticals11, Bayer Corporation12, Newbury College13
TL;DR: Sorafenib plus DEB-TACE was technically feasible, but the combination did not improve TTP in a clinically meaningful manner compared with DEB -TACE alone.
509 citations
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TL;DR: The angiogenesis biomarkers Ang2 and VEGF were independent predictors of survival in patients with advanced HCC, and none of the biomarkers tested significantly predicted response to sorafenib.
Abstract: The angiogenesis biomarkers Ang2 and VEGF were independent predictors of survival in patients with advanced HCC. In contrast, none of the biomarkers tested significantly predicted response to sorafenib.
494 citations
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TL;DR: In this phase 3 trial involving patients with HER2-low metastatic breast cancer, trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician's choice of chemotherapy.
Abstract: BACKGROUND
Among breast cancers without human epidermal growth factor receptor 2 (HER2) amplification, overexpression, or both, a large proportion express low levels of HER2 that may be targetable. Currently available HER2-directed therapies have been ineffective in patients with these "HER2-low" cancers.
METHODS
We conducted a phase 3 trial involving patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy. (Low expression of HER2 was defined as a score of 1+ on immunohistochemical [IHC] analysis or as an IHC score of 2+ and negative results on in situ hybridization.) Patients were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan or the physician's choice of chemotherapy. The primary end point was progression-free survival in the hormone receptor-positive cohort. The key secondary end points were progression-free survival among all patients and overall survival in the hormone receptor-positive cohort and among all patients.
RESULTS
Of 557 patients who underwent randomization, 494 (88.7%) had hormone receptor-positive disease and 63 (11.3%) had hormone receptor-negative disease. In the hormone receptor-positive cohort, the median progression-free survival was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician's choice group (hazard ratio for disease progression or death, 0.51; P<0.001), and overall survival was 23.9 months and 17.5 months, respectively (hazard ratio for death, 0.64; P = 0.003). Among all patients, the median progression-free survival was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician's choice group (hazard ratio for disease progression or death, 0.50; P<0.001), and overall survival was 23.4 months and 16.8 months, respectively (hazard ratio for death, 0.64; P = 0.001). Adverse events of grade 3 or higher occurred in 52.6% of the patients who received trastuzumab deruxtecan and 67.4% of those who received the physician's choice of chemotherapy. Adjudicated, drug-related interstitial lung disease or pneumonitis occurred in 12.1% of the patients who received trastuzumab deruxtecan; 0.8% had grade 5 events.
CONCLUSIONS
In this trial involving patients with HER2-low metastatic breast cancer, trastuzumab deruxtecan resulted in significantly longer progression-free and overall survival than the physician's choice of chemotherapy. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast04 ClinicalTrials.gov number, NCT03734029.).
490 citations
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TL;DR: The following Clinical Practice Guidelines will give up-to-date advice for the clinical management of patients with hepatocellular carcinoma, as well as providing an in-depth review of all the relevant data leading to the conclusions herein.
7,851 citations
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Kindai University1, University of California, Los Angeles2, Yonsei University3, University of Bologna4, California Pacific Medical Center5, Fourth Military Medical University6, Gdańsk Medical University7, University of Bordeaux8, Hannover Medical School9, Beatson West of Scotland Cancer Centre10, Eisai11, National Taiwan University12
TL;DR: Lenvatinib was non-inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma and the safety and tolerability profiles of lenvatinIB were consistent with those previously observed.
3,046 citations
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University of Navarra1, University of Hong Kong2, Kindai University3, National Taiwan University4, Seoul National University Hospital5, Goethe University Frankfurt6, University of Michigan7, Royal Free Hospital8, Asan Medical Center9, The Chinese University of Hong Kong10, Johns Hopkins University11, Bristol-Myers Squibb12, Chartered Institute of Management Accountants13
TL;DR: Durable objective responses show the potential of nivolumab for treatment of advanced hepatocellular carcinoma, and safety and tolerability for the escalation phase and objective response rate were primary endpoints.
2,908 citations
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2,777 citations
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TL;DR: This paper aims to demonstrate the efforts towards in-situ applicability of EMMARM, as to provide real-time information about concrete mechanical properties such as E-modulus and compressive strength.
2,734 citations