Boceprevir in null responders:
Response-Guided Therapy (RGT) for Boceprevir (Boc) Combination Treatment? – Results from HCV SPRINT-1
Background: HCV SPRINT-1 investigated a 4-week lead-in of PegIntron (P;1.5 mcg/kg/QW) plus Ribavirin (R;800-1400 mg/day) prior to the addition of Boc (800 mg TID) for 24 or 44 weeks. Analysis of this data may lead to RGT paradigms.
Methods: Viral response was assessed by Roche TaqMan (LLD=15 IU/ml) at multiple time points including treatment weeks 4, 8, 12, 24 and 24 weeks post-treatment (sustained virologic response; SVR). Results: Patients were all G1 (1a>1b) with 15% African-Americans, 7% cirrhotics and 90% high viral load. W8 virology was available for all 103 patients in each arm. The majority of patients (64%) became negative by week 8 and SVR rates were similar for the long (94%) and short (82%) treatment arms (p=NS). In contrast, patients who first became negative between week 8 and 16, benefited from longer therapy (SVR 79% vs 21%; p=0.004), but represented only 18% of the population. A third group never achieved undetectable HCV-RNA by W16; this group primarily comprises null responders (11/18 in 48W arm) at week 4.
Conclusions: The majority of patients (64%) had undetectable HCV-RNA after 4 weeks of triple therapy following the lead-in and had a high rate of SVR (82%) following a shortened 28-week treatment duration. Only 18% of patients first achieving undetectable HCV-RNA after week 8 and before week 16 of therapy benefited from a longer treatment regimen of 48 weeks. These data suggest that only a minority of treatment-naïve G1 patients will require more than 28 weeks of therapy, and response-guided therapy based on week-8 viral response may be a powerful predictive tool to individualize therapy. The SPRINT-2 trial is designed to prospectively confirm this treatment paradigm.
