NATAP: Pegasys in IFN/RBV Nonresponders

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Pegasys in IFN/RBV Relapsers & Nonresponders Canadian EAP

Reported by Jules Levin

These study results were reported at both EASL & DDW, April/May 2005.

….19% of previous genotype 1 IFN/RBV non-responders & 31% of previous genotype 1 IFN/RBV relapsers achieved an SVR (sustained viral response) in the Canadian Expanded Access Program…. For genotype 2/3 non-responders 35% achieved SVR, for genotype 2/3 relapsers 51% achieved SVR….Patients received Pegasys plus 800mg/day of ribavirin, suggesting response rates might have been better if the currently recommended regimen of 1000/1200 mg/day of ribavirin were used. (This EAP was initiaited before optimal treatment regimens had been established). The study investigators conclude these results “provide a strong rationale for retreating these patientsâ€.

“Peginterferon alfa-2a (40KD) (PEGASYS) plus ribavirin (COPEGUS)

in chronic hepatitis C patients who failed previous

interferon-based therapy: results of a multicentre

open-label expanded access programme in Canadaâ€

M. Sherman,1 E. Yoshida,2 M. Deschenes,3 M. Krajden,4 V. Bain,5 K. Peltekian,6 F. ,7 K. Kaita,8 S. Simonyi,9 S. Lee10

1University Health Network, Toronto General Hospital, Toronto, ON; 2Vancouver Hospital Health Sciences Centre, Vancouver, BC; 3Royal Hospital, Montreal, QC;

4British Columbia Centre for Disease Control, Vancouver, BC; 5University of Alberta, Edmonton, AB; 6QEII - Health Sciences Centre, Hepatology Services, Halifax, NS;

7The Liver and Intestinal Research Centre, Vancouver, BC; 8 Buhler Research Centre, Winnipeg, MB; 9Roche, Canada; 10Heritage Medical Research Clinic, Calgary, AB, Canada

A total of 863 patients were assigned to either 24 (genotype 2/3) or 48 weeks (genotype 1) treatment with Pegasys plus ribavirin 800mg/day.

This was open-label program conducted at 18 centers in Canada. Sustained Viral Response (SVR) was defined as <50 IU/mLHCV RNA qualitative PCR, Cobas Amplicor v. 2.0) following 24 week untreated followup period after treatment ended. All patients who received >=1 dose of study drug were included (ITT analysis).

Where documented, most previously treated patients 253/355; 71% had received combination therapy with IFN/RBV:

ITT population: (119 relapsers and 236 non-responders).

(67% of relapsers and 73% of non-responders).

BASELINE CHARACTERISTICS

--42% of patients had cirrhosis (139/33), F3/F4 in genotype 1 group; and 27% (35/93) in genotype 2/3 group.

--50-60% of patients had >500,000 IU/mL HCV RNA (viral load)

--Among genotype 1, 28% had >800,000 IU/mL. Among genotype 2/3 receiving 24 week therapy 34-42% had >800,000 IU/ml.

--BMI (kg/m2) was 26.7-28.

--57-70% were men; among 48 week treatment group (83% genotype 1): 65-70% were men. Among 24 week treatment group 98-100% were genotype 2/3 & 57-66% were men.

RESULTS

Although not mentioned directly in the posters, it appears as though growth factors (EPO for anemia) was not used for patients.

SVR TREATMENT NAÃVE PATIENTS:

55% overall

72% - genotype 2/3

39% - genotype 1

Cirrhotics: 41%

Non-cirrhotics: 50%

These responses were similar to those seen in randomized large phase III studies.

The study investigators concluded the SVR rates immediately below for non-responders & relapsers “provide a strong rationale for retreating these patientsâ€.

SVR FOR NON-RESPONDERS & RELAPSERS:

NON-RESPONDERS

Genotype 1: 20%

Genotype 2/.3: 35%

RELAPSERS

Genotype 1: 35%

Genotype 2/3: 51%

SVR RATE for PREVIOUS NON-RESPONDERS to IFN+RBV:

Genotype 1: 19% (29/149)

Genotype 2/3: 35% (7/20)

RELAPSERS:

G1: 31% (17/54)

G2/3: 52% (12/12)

Table 2. Efficacy pf Pegasys plus ribavirin 800mg/day in relapsers & non responders according to HCV genotype

SAFETY

Similar proportions of relapsers and responders receiving 48 weeks of therapy required peginterferon alfa-2a (40KD) dose modifications for neutropenia (23% vs 19%) or thrombocytopenia (7% vs 6%) and ribavirin dose modifications for anaemia (10% vs 8%) (Table 3).

The overall incidence of serious adverse events was similar in non-responders and relapsers. A total of 12 adverse events were reported in 11 of the 236 non-responders (5%) and a total of 14 adverse events were reported in 9 of 119 relapsers (8%). Overall, 10 events occurring in 9 patients were judged to be related to study treatment by the investigators.

6-12% of patients experienced anemia (<10 g/dL).

12-25% of patients experienced neutropenia grade 3 or 4.

3-8% of patients experienced thrombocytopenia (reduced platelet counts) grade 3.