Department of Gastroenterology and Hepatology, Kindai University School of Medicine, Osaka, Japan
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 , Kun Liang , Kenta Shinozaki , Chunxiao Wang , Reigetsu Yoshikawa , Paolo Abada , Ryan C. Widau , Andrew X. Zhu
Background: Intermediate-stage HCC, as defined as Barcelona Clinic Liver Cancer (BCLC) Stage B, is a heterogeneous disease in terms of liver function and tumor load. REACH (NCT01140347) and REACH-2 (NCT02435433) investigated ramucirumab (RAM) in patients (pts) with HCC after prior sorafenib (SOR), with REACH-2 enrolling only pts with baseline AFP ≥400 ng/mL. An exploratory analysis of outcomes by BCLC stage was performed. Methods: All pts had HCC (BCLC stage C or B disease refractory/not amenable to locoregional therapy), Child-Pugh A, ECOG PS 0-1, and prior SOR. Pts were randomized to RAM 8 mg/kg or Placebo (P) Q2W. A pooled meta-analysis of independent pt data (stratified by study) from REACH-2 and REACH (AFP ≥400 mg/mL) was performed. Prognosis of BCLC staging in overall survival (OS) was evaluated by multivariate Cox PH model (adjusted for baseline AFP and treatment (trt) arm); Trt effects in BCLC stage B and C by Cox PH model; median OS/PFS were estimated by Kaplan-Meier method. Objective response rate (ORR) per RECIST v1.1, disease control rate (DCR), and adverse events (AEs) were also reported by BCLC. Liver function was assessed at baseline and prior to each trt with the Albumin-Bilirubin (ALBI) linear predictor. Results: Baseline characteristics were generally balanced between trt arms in each BCLC stage. BCLC staging trended as an independent prognosis factor for OS [B v C; HR = 0.756 (0.546, 1.046)]. A consistent trt benefit for RAM v P was observed across staging (Table). Grade ≥3 AEs were consistent with observations from both individual studies; hypertension was the most frequent grade ≥3 AE. No difference in liver function, as measured by ALBI, was observed between trt arms in either BCLC stage. Conclusions: Acknowledging limitations of sample size, RAM provided a survival benefit irrespective of BCLC stage. RAM was well tolerated and did not alter liver function compared to P. Clinical trial information: NCT01140347, NCT02435433
BCLC | B | C |
---|---|---|
Pooled Population (RAM v P) |
N = 52
(RAM 30, P 22) |
N = 490
(RAM 286, P 204) |
OS median, mo | 13.7 v 8.2 | 7.7 v 4.8 |
HR (95% CI) | 0.43 (0.23, 0.83) | 0.72 (0.59, 0.89) |
PFS median, mo | 4.2 v 2.8 | 2.8 v 1.5 |
HR (95% CI) | 0.33 (0.17, 0.64) | 0.60 (0.49, 074) |
ORR, % | 17 v 5 | 4 v 1 |
DCR, % | 80 v 59 | 54 v 35 |
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Abstract Disclosures
2022 ASCO Annual Meeting
First Author: Guoliang Shao
2019 ASCO Annual Meeting
First Author: Josep M Llovet
2023 ASCO Gastrointestinal Cancers Symposium
First Author: Laura A. Dawson
2022 ASCO Gastrointestinal Cancers Symposium
First Author: Richard S. Finn