Ramucirumab (Ram) As Second-Line Treatment in Patients (Pts) with Advanced Hepatocellular Carcinoma (Hcc) Following First-Line Therapy with Sorafenib: Results from the Randomized Phase III Reach Study

Ryoo, Baek‐Yeol; Yen, Chia Jui; Kudo, Masatoshi; Poon, Ronnie T. P.; Pastorelli, Davide; Blanc, J.-F.; Chung, Hyun Cheol; Baron, Ari David; Pfiffer, Tatiana; Okusaka, Takuji; Kubáčková, Kateřina; Trojan, Jörg; Sastre, Javier; Chau, I.; Chang, Shi-Chuan; Abada, Paolo; Yang, Lifen; Schwartz, Jonathan D.; Park, J.O.

doi:10.1093/annonc/mdu438.16

Cited by 21 publications

(15 citation statements)

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“…To date, a number of mono or combination therapies have been tested as first- or second-line treatment in HCC. Phase III trials of sunitinib (a multikinase inhibitor), brivanib (VEGFR- and FGFR-inhibitor), linifanib (VEGFR and PDGFR inhibitor), erlotinib (EGFR-inhibitor) and ramucirumab (monoclonal antibody targeting VEGFR2) all failed to demonstrate superiority or noninferiority against sorafenib [20–24]. Clinically, a small fraction of tumors show dramatic response to molecular targeted agents such as sorafenib, suggesting that the response can be explained by on-target effects of the drug, modulating molecular aberrations specific to the tumors.…”

Section: Unmet Needs For Therapeutic Interventions Based On Improved mentioning

confidence: 99%

Molecular classification of hepatocellular carcinoma: potential therapeutic implications

2015

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Genomic profiling of hepatocellular carcinoma (HCC) tumors has elucidated recurrent molecular aberrations common or specific to disease etiology, patient race or geographic regions, allowing the classification of HCC tumors into subclasses sharing similar molecular and clinical characteristics. Previously reported transcriptome-based molecular subclasses have highlighted several common themes. Aggressive tumors are characterized by TP53 inactivation mutations and activation of pro-oncogenic signaling pathways, and further subclassified according to expression of stemness markers. The stemness marker-negative aggressive tumors display preferential TGF-β activation. Another group of less aggressive tumors contains a subclass characterized by CTNNB1 mutations accompanied with overexpression of liver-specific WNT targets such as GLUL. Molecular therapies selectively targeting features of the HCC subclasses have suggested their utility in enriching potential responders in clinical trials and guiding therapeutic decision-making for HCC patients.

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Section: Unmet Needs For Therapeutic Interventions Based On Improved mentioning

confidence: 99%

Molecular classification of hepatocellular carcinoma: potential therapeutic implications

2015

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“…Accordingly, a total of 11 clinical trials were considered eligible for the meta-analysis [4][5][12][13][14][15][16][17][18][19][20], including six Phase III trials and five Phase II trials. Three studies evaluated advanced gastric cancer, three studies evaluated advanced NSCLC, two studies evaluated metastatic breast cancer, one study evaluated castrate-resistant prostate cancer, one study evaluated metastatic (42%) vs 29 (45%) 8 (11.6%) vs 4 (6.2%) [13] Yoon et al [14] Doebele et al [15] Zhu et al 48 (17%) vs 12 (4%) [16] Mackey et al [19] Wilke et al [4] Fuchs et al [5] Garon et al status between 0-2 and adequate kidney, liver and bone marrow function.…”

Section: • • Search Resultsmentioning

confidence: 99%

“…Three studies evaluated advanced gastric cancer, three studies evaluated advanced NSCLC, two studies evaluated metastatic breast cancer, one study evaluated castrate-resistant prostate cancer, one study evaluated metastatic (42%) vs 29 (45%) 8 (11.6%) vs 4 (6.2%) [13] Yoon et al [14] Doebele et al [15] Zhu et al 48 (17%) vs 12 (4%) [16] Mackey et al [19] Wilke et al [4] Fuchs et al [5] Garon et al status between 0-2 and adequate kidney, liver and bone marrow function. The baseline characteristics and the number of relevant adverse events in each trial are presented in tables 1 & 2.…”

Section: • • Search Resultsmentioning

confidence: 99%

Risk of Hematological Toxicities in Patients with Solid Tumors Treated with Ramucirumab: A Meta-Analysis

Abdel‐Rahman

Elhalawani

2015

Future Oncol.

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“…Unfortunately, none of those tested so far has offered survival benefit. Table 4 displays the results of the seminal sorafenib trials and those obtained with sunitinib [105], brivanib [106], linifanib [108] and the combination of sorafenib with erlotinib [109] in first line vs. sorafenib, as well as the data in second line testing brivanib [110], everolimus [111] and ramucirumab [112] (Table 6). While these failures are disappointing, dissection of their results have provided meaningful insight to elaborate around the reasons for such negative outcomes.…”

Section: Systemic Treatmentmentioning

confidence: 99%

Liver cancer: Approaching a personalized care

Bruix

Han

Gores

et al. 2015

Journal of Hepatology

267

198

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Summary The knowledge and understanding of all aspects of liver cancer [this including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA)] have experienced a major improvement in the last decades. New laboratory technologies have identified several molecular abnormalities that, at the very end, should provide an accurate stratification and optimal treatment of patients diagnosed with liver cancer. The seminal discovery of the TP53 hotspot mutation [1,2] was an initial landmark step for the future classification and treatment decision using conventional clinical criteria blended with molecular data. At the same time, the development of ultrasound, computed tomography (CT) and magnetic resonance (MR) has been instrumental for earlier diagnosis, accurate staging and treatment advances. Several treatment options with proven survival benefit if properly applied are now available. Major highlights include: i) acceptance of liver transplantation for HCC if within the Milan criteria [3], ii) recognition of ablation as a potentially curative option [4,5], iii) proof of benefit of chemoembolization (TACE), [6] and iv) incorporation of sorafenib as an effective systemic therapy [7]. These options are part of the widely endorsed BCLC staging and treatment model (Fig. 1) [8,9]. This is clinically useful and it will certainly keep evolving to accommodate new scientific evidence. This review summarises the data which are the basis for the current recommendations for clinical practice, while simultaneously exposes the areas where more research is needed to fulfil the still unmet needs (Table 1).

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Ramucirumab (Ram) As Second-Line Treatment in Patients (Pts) with Advanced Hepatocellular Carcinoma (Hcc) Following First-Line Therapy with Sorafenib: Results from the Randomized Phase III Reach Study

Cited by 21 publications

References 0 publications

Molecular classification of hepatocellular carcinoma: potential therapeutic implications

Molecular classification of hepatocellular carcinoma: potential therapeutic implications

Risk of Hematological Toxicities in Patients with Solid Tumors Treated with Ramucirumab: A Meta-Analysis

Liver cancer: Approaching a personalized care

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