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Boceprevir Boosts Sustained Virologic Response Rate With HCV Genotype 1
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18th Conference on Retroviruses and Opportunistic Infections, February 27-March 2, 2011, Boston
Mark Mascolini
Adding boceprevir to pegylated interferon plus ribavirin (PegIFN/RBV) significantly improved sustained virologic response (SVR) rates compared with PegIFN/RBV alone in people with hard-to-treat HCV genotype 1, according to results of the 1100-person SPRINT-2 trial [1]. Both blacks and nonblacks enjoyed this SVR advantage with boceprevir, an HCV-NS3 protease inhibitor, though response rates were higher among nonblacks.
SPRINT-2 investigators randomized previously untreated people with HCV infection to one of three arms.
Four weeks of PegIFN plus weight-adjusted RBV, then:
Arm 1: Peg/IFN plus placebo through week 48
Arm 2: Peg/IFN plus boceprevir through week 28, then continued PegIFN/RBV if HCV RNA detectable during week 8 to 24, or observation only if HCV RNA undetectable during week 8 to 24
Arm 3: PegIFN/RBV plus boceprevir through week 48 regardless of HCV RNA detectability during week 8 to 24.
The researchers split study participants into two cohorts: cohort 1 included 938 nonblacks and cohort 2 included 159 blacks. The primary endpoint was proportion of people who attained SVR among those who received at least one dose of study drugs. People with detectable HCV RNA at week 24 stopped treatment.
Age averaged about 49 in cohort 1 and 51 in cohort 2. About two thirds of cohort 1 members lived in North America and the rest in Europe. Almost everyone in cohort 2 lived in North America. More than 90% in both cohorts had an HCV load above 400,000 IU/mL. Proportions with a METAVIR F3/F4 score were 7%, 8%, and 12% in arms 1, 2 and 3 of cohort 1, and 2%, 15%, and 11% in arms 1, 2, and 3 of cohort 2.
Overall SVR rates were significantly higher in boceprevir arm 2 (63%) and boceprevir arm 3 (66%) than in arm 1 (38%) (P < 0.0001 for both comparisons). Relapse rates were 22% in arm 1, 9% in arm 2, and 9% in arm 3. In nonblack cohort 1 patients, SVR rates in arms 1, 2, and 3 were 40%, 67%, and 68%. In black cohort 2 patients, SVR rates in arms 1, 2, and 3 were 23%, 42%, and 53%. Differences between arms 2 and 3 and arm 1 were statistically significant in both cohorts.
In nonblack cohort 1 patients with undetectable HCV RNA at week 8, 86% in arm 1, 89% in arm 2, and 91% in arm 3 attained SVR. Among people with at least one detectable HCV RNA between weeks 8 to 24, 74% in the two boceprevir arms attained SVR. In nonblack cohort 1 patients with at least a 1-log (10-fold) decline in HCV RNA at week 4, SVR rates were 52% in arm 1, 82% in arm 2, and 82% in arm 3.
Among nonblack patients, 27% in arm 1, 8% in arm 2, and 9% in arm 3 had to stop treatment at week 24 because of the preset stopping rule. In cohort 2 black patients, 48% in arm 1, 17% in arm 2, and 15% in arm 3 stopped treatment at week 24 because of the stopping rule.
Serious adverse event rates were 9% in arm 1, 11% in arm 2, and 12% in arm 3. Similar percentages in each treatment group stopped treatment because of adverse events: 16% in arm 1, 12% in arm 2, and 16% in arm 3. Respective proportions of patients who needed a dose change because of adverse events were 26%, 40%, and 35%. Anemia affected 49% of people randomized to boceprevir versus 29% of those in the placebo group. Dysgeusia (abnormal or metallic taste) affected 18% taking placebo, 37% taking boceprevir in arm 2, and 43% taking boceprevir in arm 3.
The SPRINT-2 team concluded that adding boceprevir to PegIFN/RBV significantly increases SVR rates in both black and nonblack patients, at the expense of a higher risk of anemia or dysgeusia. The investigators noted that SVR was comparable in people who received 48 weeks of boceprevir regardless of HCV RNA detectability during weeks 8 to 24 (arm 3) and in those who received therapy guided by HCV RNA response week 8 to 24 (arm 2).
Reference
1. Sulkowski M, Poordad F, McCone J, et al. BOC combined with P/R for treatment-naive patients with HCV genotype-1: SPRINT-2 final results. 18th Conference on Retroviruses and Opportunistic Infections. February 27-March 2, 2011. Boston. Abstract 115.
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