Response-Guided Therapy (RGT) with Boceprevir (BOC) + Peginterferon alfa-2b/Ribavirin (P/R) for Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype (G) 1
Was Similar to a 48-Wk Fixed-Duration Regimen with BOC + P/R in SPRINT-2
J. Bronowicki; J. McCone; B. R. Bacon; S. Bruno; M. P. Manns; M. S. Sulkowski; I. M. Jacobson; K. Reddy; N. Boparai; V. Sniukiene; C. A. Brass; J. K. Albrecht; F. Poordad
Background: In SPRINT-2, BOC added to P/R given for 44 wks or as RGT after a 4-wk lead-in (LI) treatment period with P/R significantly improved the sustained virologic response (SVR) in treatment-naïve G1 patients compared to standard of care. We examined whether RGT based on the HCV RNA response during Wks 8-24 for a total duration of 28 or 48 wks (but including only 24 wks of BOC from Wks 4 to Wk 28 regardless of the Wk 8-24 HCV RNA response) produced similar results to the 4-wk LI & then BOC/P/R for 44 wks.
Methods: SPRINT-2 compared a LI treatment period with P/R, followed by (1) P/R plus placebo for 44 wks (48P/R); (2) RGT: BOC/P/R for 24 wks, with an additional 20 wks of P/R alone only if HCV RNA was detected during Wks 8-24 (LI+24BOC/P/R+/-20P/R); or (3) BOC/P/R for 44 wks (LI+44BOC/P/R). Study therapy was stopped for futility in patients with detectable HCV RNA at Wk 24. The primary efficacy endpoint was the SVR in all randomized patients treated with ≥1 dose of any study medication. Non-black (Cohort 1) & black (Cohort 2) patients were enrolled & analyzed separately per protocol.
Results: In Cohort 1, the overall SVR [95%CI] was similar for RGT (66.8%) & LI+44BOC/P/R (68.5%), with a Δ=1.7% [-5.6%, 9.0%]. For the 47% of subjects in RGT arm who achieved persistently undetectable HCV RNA during Wks 8-24, the SVR was 97% after LI+24/BOC/P/R & similar to the 96% SVR for the corresponding patients receiving LI+44BOC/P/R (Table). 31% of patients in the RGT arm discontinued treatment by 28 weeks (mostly due to the 24-wk futility rule or adverse events) & were not assigned a treatment duration. For the 22% of patients in the RGT arm with detectable HCV RNA during Wks 8-24 who received >28 wks of therapy, the SVR was 74% after LI+24BOC/P/R+20P/R & matched the 74% SVR for the corresponding patients given LI+44BOC/P/R. Generally comparable results were seen in the much smaller Cohort 2.
Conclusions: RGT with LI+24BOC/P/R+/-20P/R based upon on-treatment HCV RNA response produced SVR similar to LI+44BOC/P/R. Non-black patients achieving undetectable HCV RNA on LI+BOC/P/R from Wk 8 through Wk 24 can have their treatment duration shortened from 48 wks to 28 wks.