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Ramucirumab As Second-Line Treatment
in Patients with Hepatocellular Carcinoma
(HCC) and Elevated Alpha-Fetoprotein (AFP)
Following Sorafenib: Pooled Results from Two
Global Phase 3 Studies (REACH-2 and REACH)
Josep M Llovet1, Masatoshi Kudo2, Richard Finn3, Peter R.
Galle4, Jean-Frederic Blanc5, Takuji Okusaka6, Ian Chau7,
Paolo B Abada8, Yanzhi Hsu8 and Andrew X Zhu9, (1)Icahn
School of Medicine at Mount Sinai, (2)Kindai University,
(3)University of California, (4)Department of Medicine I,
University Medical Center Mainz, Germany, (5)CHU De
Bordeaux, Hôpital Haut-Lévêque, (6)National Cancer Center
Hospital, (7)Royal Marsden Hospital, (8)Eli Lilly and Company,
(9)Massachusetts General Hospital, Harvard Medical Center
Background: Ramucirumab (RAM), a human IgG1
monoclonal antibody, inhibits activation of VEGFR2.
REACH-2 and REACH were two randomized, global, blinded,
phase 3 studies of RAM vs palcebo (PL) in patients (pts)
with HCC after prior sorafenib. REACH-2 was designed to
confirmed the benefit of RAM in the pre-specified population
of pts with baseline AFP ≥400 ng/mL observed in REACH.
The primary endpoint of REACH-2 was met demonstrating an
improved overall survival (OS), and RAM was well tolerated.
Pooled analyses of pts from REACH-2 (292) and REACH
(250) with baseline AFP ≥400 ng/mL were performed (N=316
RAM vs N=226 PL) Methods: With the exception of AFP
level, REACH-2 and REACH eligibility were similar, enrolling
HCC pts with BCLC stage C or B refractory/not amenable
to locoregional therapy, ECOG PS 0 or 1, Child-Pugh <7;
disease progression on or intolerance to sorafenib, and
adequate lab parameters. Pts received IV RAM (8 mg/kg) or
PL every 14 days and were treated until disease progression
or unacceptable toxicity. Pooled analyses were performed
at the individual pt level, stratified by study, and assessed
OS, progression-free survival (PFS), objective response rate
(ORR), safety, and pt reported symptoms (FACT-Hepatobiliary
Symptom Index-8 [FSHI-8]). Results: Pooled baseline pt
characteristics were balanced between arms including ECOG
PS, presence of macrovascular invasion, and baseline AFP.
RAM treatment significantly improved OS (median OS 8.1
mo vs 5.0 mo PL; HR 0.694; 95% CI 0.571, 0.842; p=.0002).
Improvements were observed in PFS (median PFS 2.8 mo vs
1.5 mo PL; HR 0.572; 95% CI 0.472, 0.694; p<.0001), ORR
(5.4% RAM vs 0.9% PL [p=.0040]), and disease control rate
(ORR + stable disease = 56.3% RAM vs 37.2% PL [p<.0001]).
Dose intensity was 98.3% RAM vs 99.6% PL. 9.5% of pts on
the RAM arm vs 3.6% on PL discontinued study treatment
due to treatment-related adverse events (AEs). Hypertension
(12.0% vs 3.6% PL) and hyponatremia (5.1% vs 2.2% PL)
were the only Grade (G) ≥3 treatment-emergent AEs occurring
in ≥5% in RAM. RAM treatment significantly delayed time to
deterioration of FHSI-8 (p=0.0152), including individual items
of back pain, weight loss, and pain. Conclusion: A pooled
analysis of two phase 3 trials assessing RAM as second-line
treatment in pts with HCC following first-line sorafenib and
AFP ≥400 ng/mL (REACH-2 and REACH) demonstrates a
significant and clinically meaningful benefit with a favorable
safety profile, including a benefit in pt-reported outcomes.作者: StephenW 时间: 2018-10-10 20:25