scholarly journals VESPRO: An Individual Patient Data Prospective Meta-Analysis of Selective Internal Radiation Therapy Versus Sorafenib for Advanced, Locally Advanced, or Recurrent Hepatocellular Carcinoma of the SARAH and SIRveNIB Trials

2017 ◽  
Vol 6 (2) ◽  
pp. e17 ◽  
Author(s):  
Val Gebski ◽  
Emma Gibbs ◽  
Mihir Gandhi ◽  
Gilles Chatellier ◽  
Aurelia Dinut ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiation Therapy ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Patient Data ◽  
Selective Internal Radiation Therapy ◽  
Internal Radiation ◽  
Recurrent Hepatocellular Carcinoma ◽  
Selective Internal Radiation

Nemesis: Non-inferiority meta-analysis of selective internal radiation therapy with yttrium-90 resin microspheres versus sorafenib in advanced hepatocellular carcinoma: A preliminary analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15604-e15604
Author(s):  
Marino Venerito ◽  
Maciej Pech ◽  
Ali Canbay ◽  
Rossella Donghia ◽  
Vito Guerra ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiation Therapy ◽  
Meta Analysis ◽  
Advanced Hepatocellular Carcinoma ◽  
Selective Internal Radiation Therapy ◽  
Internal Radiation ◽  
Advanced Hcc ◽  
Selective Internal Radiation ◽  
Resin Microspheres ◽  
Yttrium 90

e15604 Background: No survival benefit has been observed for selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres versus (vs.) sorafenib in patients with advanced hepatocellular carcinoma (HCC). In NEMESIS, we assessed by an individual patient data meta-analysis whether SIRT, either as monotherapy or followed by sorafenib, is non-inferior to sorafenib and compared safety profiles. Here we present preliminary data. Methods: A systematic search of MEDLINE, EMBASE, and the Cochrane Library, up to 6 December 2018, found three randomized trials comparing SIRT as monotherapy, or followed by sorafenib, to sorafenib monotherapy among patients with advanced HCC. The main outcomes were overall survival (OS) and frequency of adverse events (AEs). Survival data were pooled (fixed effect analysis). The primary population for non-inferiority analysis was the per-protocol (PP) population. The non-inferiority margin for the hazard ratio (HR) upper boundary was set at 1.08 as specified in EASL guidelines. Results: The three included trials compared sorafenib to SIRT (SIRveNIB and SARAH) or to SIRT followed by sorafenib (SORAMIC) in 1243 patients. After randomization, 23.3% vs. 7.1% of patients (p < 0.0001) did not receive the allocated intervention, and 542/608 (89.1%) vs. 418/635 (65.8%), (odds ratio [OR] 4.3, 95% CI: 3.2-5.8, p < 0.0001) completed the study without major protocol deviations (PP population), in the SIRT and sorafenib arms, respectively. Baseline characteristics of the PP population did not differ between the two comparison groups. Median OS with SIRT followed or not by sorafenib was non-inferior to sorafenib (HR 0.90, 95% CI 0.78–1.02). Treatment-related AEs grades ≥3 were reported in 109/356 (30.6%) patients who received SIRT and 197/378 (52.1%) patients in the sorafenib arm (SIRveNIB and SARAH only, p = 0.0002). Conclusions: SIRT as initial therapy for advanced HCC is non-inferior to sorafenib in OS, and offers a better safety profile.

Phase III multi-centre open-label randomized controlled trial of selective internal radiation therapy (SIRT) versus sorafenib in locally advanced hepatocellular carcinoma: The SIRveNIB study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4002-4002 ◽  
Author(s):  
Pierce H. W. Chow ◽  
Mihir Gandhi ◽  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiation Therapy ◽  
Hepatic Metastasis ◽  
Locally Advanced ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Selective Internal Radiation Therapy ◽  
Internal Radiation ◽  
Selective Internal Radiation ◽  
Internal Radiation Therapy

4002 Background: The optimal therapeutic regime for locally advanced hepatocellular carcinoma (HCC) with and without vascular invasion remains unclear. This study evaluates the efficacy of Selective Internal Radiation Therapy using SIR-Spheres yttrium-90 microspheres (Y90) versus sorafenib in Asian Barcelona Clinic Liver Cancer (BCLC) stage B and C patients without extra-hepatic metastasis. Methods: This investigator-initiated multi-center trial randomized eligible patients with locally advanced inoperable HCC to single injection of Y90 or sorafenib (oral 400mg BD) till progressive disease or unacceptable toxicity. The sample size, assuming type I error (two-sided) of 0.05 and power of 90% was 360 patients. Final analysis was planned at 266 reported deaths. Results: 360 patients (182 Y90, 178 sorafenib) were enrolled from 27 centers in 11 Asian countries. BCLC C patients without extra-hepatic metastasis comprised 41.4% of patients, 30.6% had portal vein thrombosis (PVT), 88.6% were Child-Pugh A, 57.2% were hepatitis B and 15.0% were hepatitis C. Altogether 28.6% and 9.0% of patients in the Y90 and sorafenib arms respectively failed to receive planned therapy. Intention-to-treat analysis was carried out with the overall survival (OS) in the Y90 and sorafenib arms being 8.54 and 10.58 months respectively (Hazard ratio (HR) 1.17, p =0.203). Tumour response rate (TRR) was 16.5% and 1.7% (p < 0.001) respectively. Time-to-tumor -progression (TTP) was 5.88 vs 5.36 (overall) (HR 0.93) and 6.08 vs 5.39 (liver-specific) (HR 0.91) months for Y90 and sorafenib respectively. Progression-free-survival (PFS) was 5.29 vs 5.06 (overall) (HR 0.94) and 5.85 vs 5.06 (liver-specific) (HR 0.92) months respectively. At least one severe adverse event was found in 27.7% and 50.6% of patients in the Y90 and sorafenib arms respectively. Conclusions: Asian patients with locally advanced HCC without extra-hepatic metastasis treated with Y90 have statistically significant better TRR, and fewer SAEs when compared with those treated with sorafenib. There were no statistically significant differences in OS between Y90 and sorafenib. Clinical trial information: NCT01135056.

SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma

2018 ◽  
Vol 36 (19) ◽  
pp. 1913-1921 ◽  
Author(s):  
Pierce K.H. Chow ◽  
Mihir Gandhi ◽  
Say-Beng Tan ◽  
Maung Win Khin ◽  
Ariunaa Khasbazar ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Locally Advanced ◽  
Asia Pacific ◽  
Selective Internal Radiation Therapy ◽  
Internal Radiation ◽  
Advanced Hcc ◽  
Selective Internal Radiation ◽  
Internal Radiation Therapy ◽  
Sorafenib Group ◽  
Grade 3

Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 (90Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 [27.7%]) v 82 of 162 [50.6%]; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 [3.8%] v four of 162 [2.5%] patients), abdominal pain (three [2.3%] v two [1.2%] patients), anemia (zero v four [2.5%] patients), and radiation hepatitis (two [1.5%] v zero [0%] patients). Fewer patients in the RE group (27 of 130 [20.8%]) than in the sorafenib group (57 of 162 [35.2%]) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.

Sign in / Sign up

Export Citation Format

Share Document