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Bending the Curve Trial by Trial
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REACH-2

Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased alpha-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial

Phase 3N = 292NCT02435433

Population
Patients with advanced hepatocellular carcinoma and alpha-fetoprotein of 400 ng/mL or greater who had previously received sorafenib
Design
Randomised (2:1), double-blind, placebo-controlled phase 3 trial at 92 sites in 20 countries; ramucirumab 8 mg/kg intravenously every 2 weeks or placebo, with best supportive care. Eligible patients had BCLC stage B or C disease, Child-Pugh class A, ECOG performance status 0 or 1, alpha-fetoprotein 400 ng/mL or greater, and previous first-line sorafenib. Primary endpoint overall survival; efficacy analyses by intention to treat.
Primary endpoint
OS
Arms
  • Ramucirumab plus best supportive care (experimental, n = 197): Ramucirumab 8 mg/kg intravenously every 2 weeks
  • Placebo plus best supportive care (control, n = 95): Placebo every 2 weeks
People
Zhu AX, REACH-2 study investigators
OSHR 0.710 (95% CI 0.531–0.949)Δ median OS+1.2 monthsPFSHR 0.452 (95% CI 0.339–0.603)Δ median PFS+1.2 monthsΔ ORR+4 points
Show the numbers
Results reported for REACH-2
EndpointAnalysisRamucirumab plus best supportive carePlacebo plus best supportive careEffect
OSprimarymedian follow-up 7.6 monthsZhu 2019median 8.5 months (7.0–10.6)median 7.3 months (5.4–9.1)HR 0.710 (95% CI 0.531–0.949)P=0.0199
PFSprimaryZhu 2019median 2.8 months (2.8–4.1)median 1.6 months (1.5–2.7)HR 0.452 (95% CI 0.339–0.603)P<0.0001Secondary endpoint.
ORRprimaryZhu 20195%1%P=0.1697Nine of 197 versus one of 95 patients; secondary endpoint; the difference was not statistically significant.
Results reported for REACH-2
EndpointAnalysisRamucirumab plus best supportive carePlacebo plus best supportive careEffect
OSprimarymedian follow-up 7.6 monthsZhu 2019median 8.5 months (7.0–10.6)median 7.3 months (5.4–9.1)HR 0.710 (95% CI 0.531–0.949)P=0.0199
PFSprimaryZhu 2019median 2.8 months (2.8–4.1)median 1.6 months (1.5–2.7)HR 0.452 (95% CI 0.339–0.603)P<0.0001Secondary endpoint.
ORRprimaryZhu 20195%1%P=0.1697Nine of 197 versus one of 95 patients; secondary endpoint; the difference was not statistically significant.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSPFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.710.531–0.949
PFS0.4520.339–0.603
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%05101520Months (modelled)
  • Ramucirumab plus best supportive care (experimental)
  • Placebo plus best supportive care (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsRamucirumab plus best supportive carePlacebo plus best supportive care
0100.0%100.0%
566.5%62.2%
1140.8%35.2%
1627.1%21.9%
2118.0%13.6%
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%01234567Months (modelled)
  • Ramucirumab plus best supportive care (experimental)
  • Placebo plus best supportive care (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsRamucirumab plus best supportive carePlacebo plus best supportive care
0100.0%100.0%
261.0%42.0%
437.1%17.7%
529.0%11.5%
717.7%4.8%
Primary publication: Zhu AX, Kang YK, Yen CJ, Finn RS, Galle PR, Llovet JM, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(2):282-296. PubMedDOI

Appears in

Sources

  1. Zhu AX, Kang YK, Yen CJ, Finn RS, Galle PR, Llovet JM, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(2):282-296.

    PubMedDOI