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

Guoliang Shao, Yuxian Bai, Xianglin Yuan, Xiaomin Chen, Shanzhi Gu, Kangsheng Gu, Chunhong Hu, Houjie Liang, Yabing Guo, Jufeng Wang, Chia-Jui Yen, Victor Ho-Fun Lee, Chunxiao Wang, Ryan C Widau, Wanli Zhang, Junjun Liu, Qiang Zhang, Shukui Qin, Guoliang Shao, Yuxian Bai, Xianglin Yuan, Xiaomin Chen, Shanzhi Gu, Kangsheng Gu, Chunhong Hu, Houjie Liang, Yabing Guo, Jufeng Wang, Chia-Jui Yen, Victor Ho-Fun Lee, Chunxiao Wang, Ryan C Widau, Wanli Zhang, Junjun Liu, Qiang Zhang, Shukui Qin

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.

Keywords: Advanced hepatocellular carcinoma; China; Phase 3 study; Ramucirumab; Second-line therapy.

Conflict of interest statement

VL reports grant from AstraZeneca, consulting fees from AQUILAB, and personal fees from Amgen, AstraZeneca, Boston Scientific, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Takeda; and has served on advisory boards for Amgen, AstraZeneca, Merck Sharp & Dohme, Pfizer, Takeda. CXW, RW, WLZ, JJL, and QZ are employees of, shareholders in, Eli Lilly. All other authors declare no competing interests.

© 2022 Eli Lilly and Company.

Figures

Figure 1
Figure 1
Patient flow diagram. *Patients did not meet inclusion or exclusion criteria.
Figure 2
Figure 2
Kaplan–Meier plots of overall survival and progression-free survival (Chinese patients from REACH-2). Note: Hazard ratio was estimated by an unstratified Cox proportional model with treatment group as a single covariate. Abbreviations: CI, confidence interval; HR, hazard ratio.
Figure 3
Figure 3
Estimated survival plot of overall survival adjusting for baseline AFP (Chinese patients from REACH-2). Note: Hazard ratio was estimated by an unstratified Cox proportional model with treatment group as a single covariate. Abbreviations: CI, confidence interval; HR, hazard ratio.
Figure 4
Figure 4
Kaplan–Meier plots of overall survival and progression-free survival (Pooled Chinese patients from REACH-2 and REACH with AFP≥400 ng/mL). Note: Hazard ratio was estimated by a Cox proportional model with treatment group as a single covariate, stratified by study (REACH vs REACH-2). Abbreviations: CI, confidence interval; HR, hazard ratio.

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Source: PubMed

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