Author
Philippe Merle
Other affiliations: French Institute of Health and Medical Research, University College London, Hoffmann-La Roche ...read more
Bio: Philippe Merle is an academic researcher from University of Lyon. The author has contributed to research in topics: Hepatocellular carcinoma & Sorafenib. The author has an hindex of 41, co-authored 191 publications receiving 11001 citations. Previous affiliations of Philippe Merle include French Institute of Health and Medical Research & University College London.
Papers published on a yearly basis
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TL;DR: In patients with unresectable hepatocellular carcinoma, atezolIZumab combined with bevacizumab resulted in better overall and progression-free survival outcomes than sorafenib.
Abstract: Background The combination of atezolizumab and bevacizumab showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinom...
3,085 citations
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
Memorial Sloan Kettering Cancer Center1, University College London2, National Taiwan University3, University of Southern California4, University of Ulsan5, Trakya University6, University of Bordeaux7, University of Bologna8, University of Amsterdam9, The Chinese University of Hong Kong10, University of California, San Francisco11
TL;DR: Treatment with cabozantinib resulted in longer overall survival and progression‐free survival than placebo among patients with previously treated advanced hepatocellular carcinoma, and the rate of high‐grade adverse events in the cabozaninib group was approximately twice that observed in the placebo group.
Abstract: Background Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellul...
1,471 citations
Harvard University1, Asan Medical Center2, National Cheng Kung University3, University of California, Los Angeles4, University of Barcelona5, Icahn School of Medicine at Mount Sinai6, Samsung Medical Center7, Memorial Hospital of South Bend8, Gachon University9, Eli Lilly and Company10, Kindai University11
TL;DR: Overall survival, progression-free survival, proportion of patients achieving an objective response, time to radiographic progression, safety, and time to deterioration in scores on the Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index 8 (FHSI-8) were significantly improved in the ramucirumab group compared with the placebo group.
Abstract: Summary Background Patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations have poor prognosis. We aimed to establish the efficacy of ramucirumab in patients with advanced hepatocellular carcinoma and α-fetoprotein concentrations of 400 ng/mL or higher. Methods REACH-2 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 92 hospitals, clinics, and medical centres in 20 countries. Eligible patients were aged 18 years or older and had histologically or cytologically confirmed hepatocellular carcinoma, or diagnosed cirrhosis and hepatocellular carcinoma, Barcelona Clinic Liver Cancer stage B or C disease, Child-Pugh class A liver disease, Eastern Cooperative Oncology Group (ECOG) performance statuses of 0 or 1, α-fetoprotein concentrations of 400 ng/mL or greater, and had previously received first-line sorafenib. Participants were randomly assigned (2:1) via an interactive web response system with a computer-generated random sequence to 8 mg/kg intravenous ramucirumab every 2 weeks or placebo. All patients received best supportive care. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, proportion of patients achieving an objective response, time to radiographic progression, safety, time to deterioration in scores on the Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index 8 (FHSI-8), and time to deterioration in ECOG performance status. We also pooled individual patient data from REACH-2 with data from REACH (NCT01140347) for patients with α-fetoprotein concentrations of 400 ng/mL or greater. Efficacy analyses were by intention to treat, whereas safety analyses were done in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02435433. Findings Between July 26, 2015, and Aug 30, 2017, 292 patients were randomly assigned, 197 to the ramucirumab group and 95 to the placebo group. At a median follow-up of 7·6 months (IQR 4·0–12·5), median overall survival (8·5 months [95% CI 7·0–10·6] vs 7·3 months [5·4–9·1]; hazard ratio [HR] 0·710 [95% CI 0·531–0·949]; p=0·0199) and progression-free survival (2·8 months [2·8–4·1] vs 1·6 months [1·5–2·7]; 0·452 [0·339–0·603]; p Interpretation REACH-2 met its primary endpoint, showing improved overall survival for ramucirumab compared with placebo in patients with hepatocellular carcinoma and α-fetoprotein concentrations of at least 400 ng/mL who had previously received sorafenib. Ramucirumab was well tolerated, with a manageable safety profile. To our knowledge, REACH-2 is the first positive phase 3 trial done in a biomarker-selected patient population with hepatocellular carcinoma. Funding Eli Lilly.
1,057 citations
University of California, Los Angeles1, University of Ulsan2, Kindai University3, Samsung Medical Center4, Taipei Veterans General Hospital5, Chiba University6, Pontifical Catholic University of Chile7, The Chinese University of Hong Kong8, Princess Margaret Cancer Centre9, Merck & Co.10, Harvard University11, National Taiwan University12
TL;DR: The results are consistent with those of KEYNOTE-224, supporting a favorable risk-to-benefit ratio for pembrolizumab in this population, and one-sided significance thresholds for OS and PFS did not reach statistical significance per specified criteria.
Abstract: PURPOSEPembrolizumab demonstrated antitumor activity and safety in the phase II KEYNOTE-224 trial in previously treated patients with advanced hepatocellular carcinoma (HCC). KEYNOTE-240 evaluated ...
1,056 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
TL;DR: These functionally polarized cells, and similarly oriented or immature dendritic cells present in tumors, have a key role in subversion of adaptive immunity and in inflammatory circuits that promote tumor growth and progression.
4,728 citations
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
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