Boceprevir triple therapy safely, effectively used in patients with HCV G1 infection and compensated cirrhosis

Data from a meta-analysis of 5 boceprevir (Victrelis, Merck) phase 3 clinical studies was presented at the 2013 International Liver Congress, 48th annual meeting of the European Association for the Study of the Liver, in Amsterdam.

The data showed that in 180 patients with compensated cirrhosis (METAVIR fibrosis score of F4), sustained viral response rates for patients treated with boceprevir combination therapy were 55%, compared with 17% for F4 patients treated with peginterferon and ribavirin therapy.

The meta-analysis reviewed the SPRINT-2, Anemia Management Study, RESPOND-2, PEG2a and PROVIDE studies. The primary end point was SVR, or undetectable HCV RNA 24 weeks post-therapy. Among patients with undetectable HCV RNA at TW8 (approximately 40% of all F4 patients), SVR was 89% on BOC/PR.

Investigators identified 4 baseline or on-treatment predictors of SVR in F3/F4 patients: (1) undetectable HCV-RNA at treatment week (TW) 8 (ie, after 4 weeks of P/R lead-in + 4 weeks of BOC/P/R; odds ratio (OR)=10.57; P<.0001); (2) ≥1 log10 decline in HCV-RNA at TW4 (ie, after 4 weeks of P/R lead-in; OR=2.64; P=.0053); (3) male gender (OR=2.23; P=.0141); (4) baseline HCV RNA ≤800,000 IU/mL (OR=2.55; P=.0383).

The following adverse events/laboratory changes were observed more frequently (>5% difference) in F4 patients compared with F0 – 3 in both BOC/PR and PR treatment groups: serious adverse events (SAEs), dose modifications for adverse event or anemia, infections, hemoglobin <10 g/dL, grade 2/3 thrombocytopenia and grade 3/4 neutropenia. In addition, the following adverse events/laboratory changes were observed more frequently (>5% difference) in F4 patients treated with BOC/PR compared with F4 patients treated with PR: SAEs, discontinuations for adverse events, dose modifications for anemia, infections, Hemoglobin <10 gm/dL and grade 2/3 thrombocytopenia. Three F4 and F2 patients had adverse events that may be considered to be manifestations of hepatic decompensation or severe infection.

“Recognizing that HCV treatment is not a one-size-fits-all approach, researchers identified the need to understand efficacy and safety in the cirrhotic population,” Eliav Barr, MD, vice president, Infectious Diseases, Project Leadership and Management, Merck Research Laboratories told Formulary. “Difficult to treat patient groups, such as patients with cirrhosis, are under-represented in individual HCV clinical trials, and there have been questions regarding overall benefit: risk of triple therapy in this important population.”

This data provides additional efficacy and safety data on a large number (180) F4 patients treated with boceprevir plus PR. The study is important in that it showed an overall favorable benefit: risk profile for cirrhotics,” according to Dr Barr.

“The study also identified baseline and on-treatment predictors of response that enable identification of those patients most likely to benefit from treatment (strongest predictor of achieving SVR was patients who are HCV RNA undetectable by 8 weeks of treatment (approximately 40% of all cirrhotics). On the other hand, the study also identified a subset of cirrhotics (approximately 9% of total) that do not benefit from treatment (no patients who were still HCV RNA detectable at TW8 and had not shown a 3 log reduction in HCV RNA achieved SVR).

“So this study showed an overall substantial benefit to Victrelis/PR, a manageable safety profile in compensated chirrotics, and identified treatment week 8 as an important decision point,” said Dr Barr.

“Based on an overall favorable benefit-risk profile, boceprevir triple therapy can be used safely and effectively in patients with HCV G1 infection and compensated cirrhosis,” he concluded. “Efficacy is particularly high in cirrhotic patients achieving undetectable HCV-RNA at TW8. Viral response at TW8 is especially informative in deciding to continue or discontinue treatment. Overall, based on these results, a treatment duration of 48 weeks can be recommended for cirrhotic patients.”