Dataset Information

Ramucirumab as second-line treatment in Chinese patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib (REACH-2 China): A randomised, multicentre, double-blind study.

ABSTRACT:

Background

In the global REACH-2 study, ramucirumab significantly improved overall survival (OS) compared with placebo in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP). REACH-2 China study aimed to evaluate the efficacy and safety of ramucirumab in Chinese patients with advanced HCC (NCT02435433).

Methods

REACH-2 China was a randomised, double-blind, placebo-controlled, phase 3 study done at 31 centres in China between Sep 16, 2015, and March 15, 2021. Patients with advanced HCC and AFP ≥400 ng/mL after first-line sorafenib were randomly assigned (2:1) to receive ramucirumab 8 mg/kg intravenously or placebo Q2W, until disease progression or unacceptable toxicity. The primary endpoint was OS. Efficacy was assessed per intention-to-treat, and safety in patients who received any treatment.

Findings

Of 104 Chinese patients enrolled (44 in the global study and 60 in the China extension study), 70 received ramucirumab and 34 received placebo. Median OS was 9·1 months in the ramucirumab group and 6·2 months in the placebo group (HR = 0·854 [95% CI: 0·536, 1·359]). The most common grade 3 or worse treatment-emergent adverse event were hypertension (5 [7·1%] of 70 patients in the ramucirumab group vs 1 [2.9%] of 34 in the placebo group), pneumonia (5 [7·1%] vs 1 [2·9%]), and hyponatraemia (4 [5·7%] vs 0 [0%]).

Interpretation

Ramucirumab demonstrated clinically meaningful improvement in OS compared to placebo for Chinese patients with advanced HCC and elevated AFP, although lacking statistical superiority. Ramucirumab was well tolerated, with a manageable safety profile. The results are consistent with those of the global REACH-2 study, supporting a favourable risk-benefit profile for ramucirumab in this population.

Funding

Eli Lilly and Company, USA.

SUBMITTER: Shao G

PROVIDER: S-EPMC9562926 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Ramucirumab as second-line treatment in Chinese patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib (REACH-2 China): A randomised, multicentre, double-blind study.

Shao Guoliang G Bai Yuxian Y Yuan Xianglin X Chen Xiaomin X Gu Shanzhi S Gu Kangsheng K Hu Chunhong C Liang Houjie H Guo Yabing Y Wang Jufeng J Yen Chia-Jui CJ Lee Victor Ho-Fun VH Wang Chunxiao C Widau Ryan C RC Zhang Wanli W Liu Junjun J Zhang Qiang Q Qin Shukui S

EClinicalMedicine 20221006

<h4>Background</h4>In the global REACH-2 study, ramucirumab significantly improved overall survival (OS) compared with placebo in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP). REACH-2 China study aimed to evaluate the efficacy and safety of ramucirumab in Chinese patients with advanced HCC (NCT02435433).<h4>Methods</h4>REACH-2 China was a randomised, double-blind, placebo-controlled, phase 3 study done at 31 centres in China between Sep 16, 2015, and ...[more]

PMID: 36247923

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Project description: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.

Project description:IntroductionCabozantinib and ramucirumab are approved for the treatment of adults with hepatocellular carcinoma (HCC) following prior sorafenib treatment; ramucirumab is restricted to use in patients with serum alpha-fetoprotein (AFP) ≥ 400 ng/mL. This matching-adjusted indirect comparison evaluated the efficacy and safety of both drugs after sorafenib in patients with HCC and AFP ≥ 400 ng/mL.MethodsIndividual patient data (IPD) from the CELESTIAL trial (cabozantinib) and population-level data from the REACH-2 trial (ramucirumab) were used. To align with REACH-2, the CELESTIAL population was limited to patients who received first-line sorafenib only and had baseline serum AFP ≥ 400 ng/mL. The IPD from CELESTIAL were weighted to balance the distribution of 11 effect-modifying baseline characteristics with those of REACH-2. Overall survival (OS; primary endpoint) and progression-free survival (PFS) were compared for the CELESTIAL (matching-adjusted) and REACH-2 populations using weighted Kaplan-Meier (KM) curves and parametric (OS, Weibull; PFS, log-logistic) modeling. Rates of treatment-related adverse events (TRAEs) and TRAE-related discontinuations were also compared.ResultsAfter matching and weighting, baseline characteristics were balanced between populations (REACH-2, N = 292; CELESTIAL, effective sample size = 105). Weighted KM estimates for OS (median [95% CI]) were not significantly different between cabozantinib and ramucirumab (10.6 [9.5-17.3] months versus 8.7 [7.3-10.8] months; p = 0.104), but PFS was significantly longer for cabozantinib than for ramucirumab (5.5 [4.6-7.4] months versus 2.8 [2.7-4.1] months; p = 0.016). Parametric modeling results were consistent with the weighted KM analysis. Rates of some grade 3 or 4 TRAEs were lower with ramucirumab than with cabozantinib; however, TRAE-related discontinuation rates were similar (p = 0.271).ConclusionIn this MAIC, cabozantinib significantly prolonged median PFS compared with ramucirumab after prior sorafenib treatment in patients with HCC and AFP ≥ 400 ng/mL; rates of some grade 3 or 4 TRAEs were lower with ramucirumab than cabozantinib but related discontinuation rates were not significantly different between treatments.Trial registrationClinical trials.gov identifiers: CELESTIAL trial (NCT01908426) and REACH-2 trial (NCT02435433). These slides can be retrieved under Electronic Supplementary Material.

Dataset Information

Ramucirumab as second-line treatment in Chinese patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib (REACH-2 China): A randomised, multicentre, double-blind study.

Background

Methods

Findings

Interpretation

Funding

Publications

Ramucirumab as second-line treatment in Chinese patients with advanced hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib (REACH-2 China): A randomised, multicentre, double-blind study.

Similar Datasets

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