Evidence map›Paper›PMID 34721507›Full record

ArticleLiver cancer2021

Ramucirumab for Patients with Intermediate-Stage Hepatocellular Carcinoma and Elevated Alpha-Fetoprotein: Pooled Results from Two Phase 3 Studies (REACH and REACH-2).

Masatoshi Kudo, Richard S Finn, Manabu Morimoto, Kun-Ming Rau, Masafumi Ikeda, Chia-Jui Yen, Peter R Galle, Josep M Llovet, Bruno Daniele, Ho Yeong Lim and 8 more

Open access · greenAbstract read
In one paragraph

Article in Liver cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.8field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 7 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 11 institutions in 5 countries.

Masatoshi KudoDepartments of Gastroenterology and Hepatology, Kindai University, Osaka, Japan.
Richard S FinnGeffen School of Medicine, University of California, Los Angeles, California, USA.
Manabu MorimotoKanagawa Cancer Center, Yokohama, Japan.
Kun-Ming RauChang Gung Memorial Hospital - Kaohsiung Branch, Kaohsiung City, Taiwan.
Masafumi IkedaDepartment of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Chia-Jui YenDepartment of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Peter R GalleDepartment of Internal Medicine, Mainz University Medical Center, Mainz, Germany.
Josep M LlovetMount Sinai Liver Cancer Program, Department of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Bruno DanieleOspedale del Mare, Naples, Italy.
Ho Yeong LimSamsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea.
David W McIlwainEli Lilly and Company, Indianapolis, Indiana, USA.
Reigetsu YoshikawaEli Lilly Japan K.K., Kobe, Japan.
Kenichi NakamuraEli Lilly Japan K.K., Kobe, Japan.
Kun LiangEli Lilly and Company, Indianapolis, Indiana, USA.
Chunxiao WangEli Lilly and Company, Indianapolis, Indiana, USA.
Paolo AbadaEli Lilly and Company, Indianapolis, Indiana, USA.
Ryan C WidauEli Lilly and Company, Indianapolis, Indiana, USA.
Andrew X ZhuMassachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.
Eli Lilly (United States) · USIcahn School of Medicine at Mount Sinai · USJohannes Gutenberg University Mainz · DEKanagawa Cancer CenterKaohsiung Chang Gung Memorial Hospital · TWKindai University · JPMassachusetts General Hospital · USNational Cancer Center Hospital East · JPNational Cheng Kung University Hospital · TWSamsung Medical Center · KRUniversity of California, Los Angeles · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIntermediate-stage hepatocellular carcinoma (HCC), as defined by Barcelona Clinic Liver Cancer (BCLC) stage B, is heterogeneous in terms of liver function and tumor burden. REACH and REACH-2 investigated ramucirumab in patients with HCC after prior sorafenib, with REACH-2 enrolling only patients with baseline α-fetoprotein (AFP) ≥400 ng/mL. An exploratory analysis of outcomes by BCLC stage was performed.

methodsA pooled meta-analysis of independent patient data (stratified by study) from REACH (AFP ≥ 400 ng/mL) and REACH-2 was performed. All patients had Child-Pugh A, Eastern Cooperative Oncology Group performance status 0-1, prior sorafenib treatment, and either HCC BCLC stage B (refractory/not amenable to locoregional therapy) or BCLC stage C. Patients were randomized to ramucirumab 8 mg/kg or placebo every 2 weeks. Median overall survival (OS) and progression-free survival were estimated by the Kaplan-Meier method. Treatment effects in BCLC stage B and C were evaluated by Cox proportional-hazards model; prognosis of BCLC staging for OS was evaluated by multivariate Cox proportional-hazards model. Tumor responses were evaluated according to Response Evaluation in Solid Tumors v1.1. Liver function was assessed with albumin-bilirubin score.

resultsBaseline characteristics were generally balanced between treatment arms in each BCLC stage. BCLC staging trended as an independent prognostic factor for OS (B vs. C; hazard ratio [HR] 0.756 [95% CI 0.546-1.046]). Consistent treatment benefit was observed for ramucirumab versus placebo across BCLC stages. Median OS for ramucirumab versus placebo was 13.7 versus 8.2 months; HR (95%): 0.43 (0.23-0.83) and 7.7 versus 4.8 months; HR (95%): 0.72 (0.59-0.89) for BCLC stage B and C, respectively. Adverse events (AEs) were consistent with observations from both studies; hypertension was the most frequent grade ≥3 AE. Liver function was preserved throughout the study and similar between treatment arms in both BCLC stages.

conclusionsRamucirumab provided a better survival benefit irrespective of BCLC stage and was well tolerated without compromising liver function during treatment.

Indexed as

Barcelona clinic liver cancer stageRamucirumabα-fetoprotein

Identifiers

PMID34721507
PMCPMC8527922
OpenAlexW3004536193

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.